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매일 고통과 함께 눈을 뜨는 아침도,

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엔브렐Ⓡ 제품설명서 전문의약품[원료약물의 분량] 프리필드시린지 중 에타너셉트 25㎎, 50㎎ [주성분] 에타너셉트(TNFR : Fc) [성상] 무색투명 또는 유백색내지 연한 황색의 액이 충진된 프리필드시린지 [효능·효과] •성인 : 1. 류마티스관절염 - 메토트렉세이트를 포함한 DMARDs (Disease-Modifying anti Rheumatic Drugs)에 반응이 적절하지 않은 중등도에서 중증의 성인 활동성 류마티스관절염에 단독 또는 메토트렉세이트와 병용투여. - 메토트렉세이트에 내약성이 없거나, 메토트렉세이트 치료를 지속하기 부적절한 경우 단독투여. - 이전에 메토트렉세이트로 치료받지 않은 중증의 활동성 및 진행성 류마티스관절염. – 류마티스관절염 환자에 단독 또는 메토트렉 세이트와의 병용투여시, X선으로 측정했을 때 질환과 관련된 구조적 손상 진행의 지연. 2. 건선성 관절염 - 이전에 DMARDs (Disease-Modifying anti Rheumatic Drugs)에 대한 반응이 적절하지 않은 활동성 및 진행성 건선성 관절염. 3. 축성 척추관절염 - 강직성 척추염 : 기존 치료에 대한 반응이 적절하지 않은 중증의 강직성 척추염. - 방사선상으로 확인되지 않는 축성척추관절염 : 방사선상으로 확인되지 않으나, CRP 상승 및/또는 MRI와 같은 객관적인 염증 징후를 보이는 중증 축성 척추관절염. 비스테로이드성 항염증 약물(NSAIDs)에 반응이 적절하지 않은 환자에게 사용. 4. 건선 – 싸이클로스포린, 메토트렉세이트 또는 PUVA를 포함한 전신 치료요법에 대해 반응이 없거나 금기이거나 내약성이 없는 중등도 또는 중증의 건선. • 소아 : 1. 소아 특발성 관절염 - 메토트렉세이트에 대한 반응이 적절하지 않거나 또는 내약성이 없는 2세 이상의 소아 및 청소년의 다수 관절염 (류마티스 인자 양성 또는 음성) 및 확장성 소수 관절염(Extended Oligoarthritis)- 메토트렉세이트에 대한 반응이 적절하지 않거나 또는 내약성이 없는 12세 이상의 청소년의 건선성 관절염 - 기존 치료요법에 반응이 적절하지 않거나 내약성이 없는 12세 이상의 청소년의 골부착부위염 관련 관절염 [용법·용량] ○ 성인(18세 이상): 1. 류마티스관절염, 건선성 관절염, 강직성 척추염 : 1회 25 mg을 주 2회 피하주사 하거나 1회 50 mg을 주 1회 피하주사한다. 2. 건선 : 1회 25㎎을 주 2회 피하 주사 하거나 1회 50㎎을 주 1회 피하주사한다. 또는, 1회 50㎎을 주 2회 12주까지 피하주사하고, 필요한 경우 그 이후에 1회 25㎎을 주 2회 피하주사하거나 1회 50 mg을 주 1회 피하주사한다. 이 약의 투여는 건선이 없어질 때까지(최대 24주까지) 계속되어야 한다. 일부 성인 환자에 있어, 24주 이상의 지속 치료가 적절할 수 있다. 12주 후에도 아무런 반응이 없는 환자의 경우에는 투약을 중단해야 한다. 이 약의 재투여가 필요한 경우, 투여기간에 대한 위의 지침을 따라야 하며, 1회 25 mg을 주 2회 피하주사하거나 1회 50 mg을 주 1회 피하주사한다. 환자는 의사의 판단과 개별 환자의 필요에 따라 연속적 또는 간헐적으로 치료받을 수 있다. 간헐적 치료 시, 최초 주기 이후 치료 주기에는 1회 25 mg을 주 2회 피하주사 하거나 1회 50㎎을 주 1회 피하 주사한다. ○ 소아 : 소아 환자에서 이 약의 투여 용량은 체중을 기준으로 한다. 체중이 62.5 kg 미만인 환자는 엔브렐주사 25 ㎎ /mL 제제를 사용하여 정확하게 ㎏당 투여용량(㎎ )을 투여해야만 한다. 체중이 62.5 kg 이상의 환자는 정해진 용량의 프리필드시린지를 사용할 수 있다. 1. 소아 특발성 관절염(2세-17세) : 1회 kg 당 0.4 mg (1회 최대 25㎎ 까지)을 주 2회(3-4일 간격으로) 피하주사하거나 1회 ㎏ 당 0.8 ㎎ (1회 최대 50 mg까지)을 주 1회 피하주사한다. 4개월 후에도 아무런 반응이 없는 환자의 경우에는 투약을 중단해야 한다. [사용상의 주의사항] 1. 경고 1)감염 : 이 약 사용으로 심각한 감염증, 패혈증, 결핵 및 다른 기회감염증이 보고되었다. 감염증 중 일부는 치명적이었다. 이는 박테리아, 미코박테리아, 진균, 바이러스 및 프로토조아를 포함한 기생충에 의한 것이었다. 2) 결핵 : 이 약을 포함하여 TNF 저해제를 투여제 받는 환자에서 파종성(속립) 결핵 및 폐외결핵(폐막, 림프절 등)이 보고되었다. 3) 아나킨라(Anakinra)와의 병용치료: 이 약과 아나킨라(Anakinra)를 병용투여한 24주간의 임상시험에서 두 약물을 병용투여한 환자의 7%에서 중증의 감염이 나타났으며 이 약 단독투여군에서는 나타나지 않았다. 4) 신경계 이상: 이 약 및 다른 TNF 저해제 투여 시 드물게 중추신경계(CNS) 탈수초성 질환의 발생 및 악화가 나타날 수 있으며 일부에서는 정신적 상태의 변화를 나타내었고 일부에서는 영구적인 불구가 나타났다. 5) 혈액학적 이상반응: 이 약을 투여 받은 환자에서 재생불량성 빈혈이 매우 드물게, 범혈구감소증은 드물게 보고되었다. 6) 악성 종양 및 림프구 증식질환: - 고형 및 조혈 악성종양(피부암 제외) : 이 약의 임상시험에서 대조군에 비해 TNF 저해제 투여군에서 더 많은 림프종이 발생하였다. – 피부암 : TNF 저해제를 사용한 환자들에게서 흑색종 및 비흑색종 피부암(NMSC)이 보고되었다. - 베게너씨 육아종증(Wegener's granulomatosis) : 180명의 베게너씨 육아종증 환자 대상 위약 대조 시험에서 89명이 표준요법(사이클로포스파미드, 메토트렉세이트, 고용량 스테로이드 포함)에 이 약을 추가하여 평균 25개월간 투여 받았으며, 위약을 투여 받은 환자보다 이 약을 투여 받은 환자에서 치료적 효과를 보여주지 못했다. 여러 가지 형태의 비 피부성 고형 악성종양의 발생빈도가 대조군보다 이 약을 투여 받은 환자군에서 높게 나타났다. 7) B형 간염 재활성화 : B형 간염 바이러스(HBV) 감염 기왕력이 있는 환자에서 이 약을 포함한 TNF 저해제 병용 투여시, B형 간염 바이러스 재활성화가 보고되었고, 일부는 치명적인 경우가 있었다. 8)울혈성 심부전 : 이 약을 투여받은 환자에서 확인할 수 있는 발생요인과 관계없이 울혈성 심부전을 악화시킨다는 보고가 시판 후 조사에서 보고되었다. 9) 주사기의 고무 마개는 라텍스(건조천연고무)를 함유하고 있으므로, 라텍스 과민성 또는 그 가능성이 있는 자가 다루거나 투여 받을 경우에는 과민반응을 유발할 수 있다. 2. 금기 1) 이 약 및 이 약 성분에 과민증 환자 2) 패혈증 또는 패혈증의 위험이 있는 환자 3) 결핵을 포함하여 만성 또는 국소 감염을 포함한 활성 감염이 있는 환자(이 약의 투여를 시작하지 않는다.) 3. 신중한 투여 1) 탈수초성 질환(다발성 경화증 등) 및 병력이 있는 환자 2) 울혈성 심부전 환자. 4. 유해사례 : 감염(상기도 감염, 기관지염, 방광염, 피부감염 포함), 주사부위 반응(홍반, 가려움, 통증, 종창, 출혈, 타박상 포함)이 임상시험에서 매우 흔하게(≥1/10) 보고되었다. 이 약과 위약을 비교하는 이중 눈가림 임상시험에서 주사부위 반응은 이 약 치료군에서 가장 흔한 유해사례였다. 제품설명서 개정년월일 : 2015. 08. 31

엔브렐은 타TNF* 제제와 비교 시 결핵 발생률이 가장 낮았습니다.2, a* Adalimumab, lnfliximab

엔브렐은 10여 년간의 축적된 임상 경험으로 지속적 효과와 우수한 내약성을 확인하였습니다.1

KENB-1510-05

[주요 안전성 정보] 엔브렐Ⓡ 투여 시 심각한 감염증, 패혈증, 결핵 및 다른 기회감염증이 보고되었습니다.3Study design a. 결핵 위험도가 중간인 지역에서 항 TNF 치료 후 결핵의 발생률, 약물과 질병 간 위험도를 비교하기 위해 실시된 연구. 한국의 건강보험심사평가원 데이터베이스를 이용하여 2005~2009년 TNF 억제제를 처방받은 환자 총 8,421명을 대상으로 함.

References 1. Weinblatt M, et al. Safety and efficacy of etanercept beyond 10 years of therapy in North American patients with early and longstanding rheumatoid arthritis. Arthritis Care Res 2011;63:373–382. 2. Jung SM, Ju JH, Park MS,et al. Risk of tuberculosis in patients treated with anti-tumor necrosis factor therapy: a nationwide study in South Korea, a country with an intermediatetuberculosis burden. Int J Rheum Dis. 2015 Mar;18(3):323-30. 3. 엔브렐(etanercept). 제품설명서. Pfizer Inc. Revised 26/1/2015.

Official Journal of Korean College of Rheumatology

Journal of Rheumatic Diseases

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JOURNAL OF RHEUMATIC DISEASES

대한류마티스학회 임원명단

자문위원 김 기 용 (울산의대) 김 동 수 (연세의대) 김 동 집 (가톨릭의대)

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김 광 남 (한림의대) 김 진 석 (제주의대) 류 완 희 (전북의대)

민 준 기 (가톨릭의대) 박 시 복 (한양의대) 서 창 희 (아주의대)

이 영 호 (고려의대) 이 지 수 (이화의대) 이 창 근 (울산의대)

임 군 일 (동국의대) 정 원 태 (동아의대) 홍 승 재 (경희의대)

감 사 박 원 (인하의대) 배상철 (한양의대)

(가나다순)

pp


대한류마티스학회 위원회명단

총무이사 김 태 환 (한양의대)

총무위원 김 성 규 (대구가톨릭의대) 이 은 영 (서울의대) 최 성 재 (고려의대)

재무이사 이 상 헌 (건국의대)

재무위원 박 경 수 (가톨릭의대) 서 영 일 (한림의대) 주 지 현 (가톨릭의대)

편집이사 전 재 범 (한양의대)

편집간사 김 용 길 (울산의대)

편집위원 강 성 욱 (충남의대) 민 준 기 (가톨릭의대) 박 민 찬 (연세의대) 박 성 훈 (대구가톨릭의대)

박 용 욱 (전남의대) 이 영 호 (고려의대) 이 재 준 (성균관의대) 최 찬 범 (한양의대)

학술이사 차 훈 석 (성균관의대)

학술간사 곽 승 기 (가톨릭의대)

학술위원 문 영 완 (성균관의대) 박 민 찬 (연세의대) 성 윤 경 (한양의대) 이 명 수 (원광의대)

이 상 일 (경상의대) 이 윤 종 (서울의대) 이 창 근 (울산의대)

국제이사 김 완 욱 (가톨릭의대)

국제간사 김 인 제 (이화의대)

국제위원 김 기 조 (가톨릭의대) 김 성 수 (울산의대) 박 용 욱 (전남의대) 이 상 훈 (경희의대)

이 은 봉 (서울의대) 정 영 옥 (한림의대)

보험이사 김 현 아 (한림의대)

보험간사 윤 보 영 (인제의대) 홍 승 재 (경희의대)

보험위원 강 태 영 (연세대원주의대) 김 태 종 (전남의대) 김 현 숙 (순천향의대) 민 도 준 (민도준내과)

박 민 찬 (연세의대) 박 성 환 (가톨릭의대) 서 영 일 (한림의대) 심 승 철 (충남의대)

엄 완 식 (한양류마엄완식내과) 윤 종 현 (가톨릭의대) 이 성 원 (동아의대) 장 대 국 (장대국내과)

주 지 현 (가톨릭의대)

홍보이사 심 승 철 (충남의대)

홍보간사 최 찬 범 (한양의대)

홍보위원 강 은 하 (서울의대) 김 상 현 (계명의대) 박 경 수 (가톨릭의대) 박 동 진 (전남의대)

신 기 철 (서울의대) 이 명 수 (원광의대) 허 진 욱 (을지의대) 홍 승 재 (경희의대)

교육연구이사 유 빈 (울산의대)

교육연구간사 윤 종 현 (가톨릭의대)

교육연구위원 김 근 태 (고신의대) 김 상 현 (계명의대) 이 창 훈 (원광의대) 서 창 희 (아주의대)

송 정 수 (중앙의대) 이 상 일 (경상의대) 차 훈 석 (성균관의대)

임상연구이사 이 신 석 (전남의대)

임상연구간사 최 성 재 (고려의대)

임상연구위원 강 성 욱 (충남의대) 곽 승 기 (가톨릭의대) 김 성 규 (대구가톨릭의대) 김 현 아 (아주의대)

남 언 정 (경북의대) 박 용 범 (연세의대) 성 윤 경 (한양의대) 신 기 철 (서울의대)

이 재 준 (성균관의대) 이 창 훈 (원광의대) 전 찬 홍 (순천향의대)

정보이사 송 정 수 (중앙의대)

정보간사 권 성 렬 (인하의대)

정보위원 고 혁 재 (가톨릭의대) 김 성 수 (울산의대) 나 성 수 (순천향의대) 안 중 경 (성균관의대)

이 상 원 (연세의대) 이 승 근 (부산의대) 이 은 영 (서울의대) 이 창 근 (울산의대)

채 지 영 (분당제생병원) 최 상 태 (중앙의대) 허 진 욱 (을지의대)

의료정책이사 백 한 주 (가천의대)

의료정책간사 이 은 봉 (서울의대)

의료정책위원 김 건 우 (대구파티마병원) 문 기 원 (강원의대) 서 미 령 (가천의대) 성 윤 경 (한양의대)

유 종 진 (한림의대) 윤 종 현 (가톨릭의대) 이 지 수 (이화의대) 임 철 현 (국군수도병원)

(가나다순)

pp


List of Korean College of Rheumatology Executive Directors

Advisory Board Key-yong Kim (Univ. of Ulsan), Dong Soo Kim (Yonsei Univ.)

Dong-Jip Kim (Catholic Univ.), Mok-Hyun Kim (Hanyang Univ.)

Think-You Kim (Hanyang Univ.), Joong-Gon Kim (Seoul National Univ.)

Ho-Youn Kim (Ho Youn Kim’s Clinic), Myung-Sang Moon (Halla General Hosp.)

Hun-Ki Min (Seoul National Univ.), Byeong Mun Park (Gwangmyeong Seongae Hosp.)

Dae-Hyun Yoo (Hanyang Univ.), Myung-Chul Yoo (Kyung Hee Univ.)

Soo-Kon Lee (CHA Univ.), Yun-Woo Lee (Withus Medical Clinic)

Duke Whan Chung (Kyung Hee Univ.), Young Kil Choi (Kangnam CHA Hosp.)

Il-Yong Choi (Hanyang Univ.)

President Yeong-Wook Song (Seoul National Univ.)

Chairman of the Board Eun-Mi Koh (Sungkyunkwan Univ.)

Director of Planning Sung-Hwan Park (Catholic Univ.), Jung-Yoon Choe (Catholic Univ. of Daegu)

Executive Secretary Tae-Hwan Kim (Hanyang Univ.)

Director of Finance Sang-Heon Lee (Konkuk Univ.)

Director of Editorial Board Jae-Bum Jun (Hanyang Univ.)

Director of Academic Affairs Hoon-Suk Cha (Sungkyunkwan Univ.)

Director of International Cooperation Wan-Uk Kim (Catholic Univ.)

Director of Insurance Hyun Ah Kim (Hallym Univ.)

Director of Public Relation Seung-Cheol Shim (Chungnam National Univ.)

Director of Education & Research Bin Yoo (Univ. of Ulsan)

Director of Clinical Trials Shin-Seok Lee (Chonnam National Univ.)

Director of Medical Information Jung Soo Song (Chung-Ang Univ.)

Director of Health Policy Affairs Han-Joo Baek (Gachon Univ.)

Director at Large Young-Wan Moon (Sungkyunkwan Univ.), Young-Beom Park (Yonsei Univ.)

Gwan Gyu Song (Korea Univ.), Tae Seok You (YTS Rheumatology Clinic)

Eun Bong Lee (Seoul National Univ.)

Board Members Seong Wook Kang (Chungnam National Univ.), Young Mo Kang (Kyungpook National Univ.)

Hyun Sik Gong (Seoul National Univ.), Kwang-Nam Kim (Hallym Univ.)

Jinseok Kim (Jeju National Univ.), Wan-Hee Yoo (Chonbuk National Univ.)

Jun-ki Min (Catholic Univ.), Si-Bog Park (Hanyang Univ.)

Chang-Hee Suh (Ajou Univ.), Young-Ho Lee (Korea Univ.)

Jisoo Lee (Ewha Womans Univ.), Chang Keun Lee (Univ. of Ulsan)

Gun-Il Im (Dongguk Univ.), Won Tae Chung (Dong-A Univ.)

Seung-Jae Hong (Kyung Hee Univ.)

Auditor Won Park (Inha Univ.), Sang Cheol Bae (Hanyang Univ.)

pp


List of Korean College of Rheumatology Executive Directors

Executive Secretary Committee Tae-Hwan Kim (Hanyang Univ.) (Chairman)Seong-Kyu Kim (Catholic Univ. of Daegu), Eun Young Lee (Seoul National Univ.)Sung Jae Choi (Korea Univ.)

Finance Committee Sang-Heon Lee (Konkuk Univ.) (Chairman)Kyung-Su Park (Catholic Univ.), Young-Il Seo (Hallym Univ.)Ji Hyeon Ju (Catholic Univ.)

Editorial Committee Jae-Bum Jun (Hanyang Univ.) (Chairman)Yong-Gil Kim (Univ. of Ulsan) (Executive Secretary)Seong Wook Kang (Chungnam National Univ.), Jun-ki Min (Catholic Univ.)Min-Chan Park (Yonsei Univ.), Sung Hoon Park (Catholic Univ. of Daegu)Wong-Wook Park (Chonnam National Univ.), Young-Ho Lee (Korea Univ.)Jaejoon Lee (Sungkyunkwan Univ.), Chan-Bum Choi (Hanyang Univ.)

Academic Affairs Committee Hoon-Suk Cha (Sungkyunkwan Univ.) (Chairman)Seung-Ki Kwok (Catholic Univ.) (Executive Secretary)Young-Wan Moon (Sungkyunkwan Univ.), Min-Chan Park (Yonsei Univ.)Yoon-Kyoung Sung (Hanyang Univ.), Myeung Su Lee (Wonkwang Univ.)Sang-il Lee (Gyeongsang National Univ.), Yun-Jong Lee (Seoul National Univ.)Chang Keun Lee (Univ. of Ulsan)

International Cooperation Committee Wan-Uk Kim (Catholic Univ.) (Chairman)In Je Kim (Hallym Univ.) (Executive Secretary)Ki-Jo Kim (Catholic Univ.), Sung Soo Kim (Univ. of Ulsan)Wong-Wook Park (Chonnam National Univ.), Sang-Hoon Lee (Kyung Hee Univ.)Eun Bong Lee (Seoul National Univ.), Young-Ok Jung (Hallym Univ.)

Insurance Committee Hyun Ah Kim (Hallym Univ.) (Chairman)Bo-Young Yoon (Inje Univ.), Seung-Jae Hong (Kyung Hee Univ.) (Executive Secretary)Tae-Young Kang (Yonsei Univ., Wonju College of Medicine), Tae-Jong Kim (Chonnam National Univ.)Hyun-Sook Kim (Soonchunhyang Univ.), Do-June Min (Dr. Min Clinic)Min-Chan Park (Yonsei Univ.), Sung-Hwan Park (Catholic Univ.)Young-Il Seo (Hallym Univ.), Seung-Cheol Shin (Chungnam National Univ.)Wan-Sik Uhm (Uhm's Hanyang Rheumatism Clinic), Chong-Hyeon Yoon (Catholic Univ.)Sung Won Lee (Dong-A Univ.), Dae-Kook Chang (Dr. Chang's Rheumatism Clinic)Ji Hyeon Ju (Catholic Univ.)

Public Relation Committee Seung-Cheol Shim (Chungnam National Univ.) (Chairman)Chan-Bum Choi (Hanyang Univ.) (Executive Secretary)Eun Ha Kang (Seoul National Univ.), Sang-Hyun Kim (Keimyung Univ.)Kyung-Su Park (Catholic Univ.), Dong-Jin Park (Chonnam National Univ.)Kichul Shin (Seoul National Univ.), Myeung Su Lee (Wonkwang Univ.)Jin-Wuk Hur (Eulji Univ.), Seung-Jae Hong (Kyung Hee Univ.)

Education & Research Committee Bin Yoo (Univ. of Ulsan) (Chairman)Chong-Hyeon Yoon (Catholic Univ.) (Executive Secretary)Geun Tae Kim (Kosin Univ.), Sang-Hyon Kim (Keimyung Univ.)Chang Hoon Lee (Wonkwang Univ.), Chang-Hee Suh (Ajou Univ.)Jung-Soo Song (Chung-Ang Univ.), Sang-il Lee (Gyeongsang National Univ.)Hoon-Suk Cha (Sungkyunkwan Univ.)

Clinical Trials Committee Shin-Seok Lee (Chonnam National Univ.) (Chairman)Sung Jae Choi (Korea Univ.) (Executive Secretary)Seong Wook Kang (Chungnam National Univ.), Seung-Ki Kwok (Catholic Univ.)Seong-Kyu Kim (Catholic Univ. of Daegu), Hyoun-Ah Kim (Ajou Univ.)Eon Jeong Nam (Kyungpook National Univ.), Yong-Beom Park (Yonsei Univ.)Yoon-Kyoung Sung (Hanyang Univ.), Kichul Shin (Seoul National Univ.)Jaejoon Lee (Sungkyunkwan Univ.), Chang Hoon Lee (Wonkwang Univ.)Chan Hong Jeon (Soonchunhyang Univ.)

Medical Information Committee Jung Soo Song (Chung-Ang Univ.) (Chairman)Seong Ryul Kwon (Inha Univ.) (Executive Secretary)Hyeok-Jae Ko (Catholic Univ.), Sung Soo Kim (Univ. of Ulsan)Seong-Su Nah (Soonchunhyang Univ.), Joong Kyoung Ahn (Sungkyunkwan Univ.)Sang-Won Lee (Yonsei Univ.), Seung-Geun Lee (Pusan National Univ.)Eun Young Lee (Seoul National Univ.), Chang Keun Lee (Univ. of Ulsan)Ji Young Chai (Bundang Jasang General Hosp.), Sang Tae Choi (Chung-Ang Univ.)Jin-Wuk Hur (Eulji Univ.)

Health Policy Committee Han-Joo Baek (Gachon Univ.) (Chairman)Eun Bong Lee (Seoul National Univ.) (Executive Secretary)Gun-Woo Kim (Daegu Fatima Hosp.), Kiwon Moon (Kangwon National Univ.)Miryoung Seo (Gachon Univ.), Yoon-Kyoung Sung (Hanyang Univ.)Jongjin Yoo (Hallym Univ.), Chong-Hyeon Yoon (Catholic Univ.)Jisoo Lee (Ewha Womans Univ.), Churl Hyun Im (Korean Armed Forces Capital Hosp.)

•Date: May 20 (Fri)∼21 (Sat), 2016 •Venue: Nine Tree Convention Gwanghwamun, Seoul, Korea

PRO GRAM

May 20 (Fri), 2016

Grand Ballroom 1 + 2

09:00-09:50 Plenary Session I - International Free Paper Session (E) Chairs: Eun-Mi Koh (Sungkyunkwan Univ., Korea)

Seung-Cheol Shim (Chungnam National Univ., Korea)

O-20-01 Urinary Interleukin-6 as a Predictor of Radiographic

Progression in Rheumatoid Arthritis: A 3-Year EvaluationYune-Jung Park (The Catholic Univ., Korea)

O-20-02 Baseline Autoantibodies Preferentially Impact

Abatacept Efficacy in Patients with RA Who are Biologic Naïve: 6-Month Results from a Real-World, International, Prospective Study

Manuela Le Bars (Bristol-Myers Squibb, France)

O-20-03 The Effect of Medication on Development

of Cardiovascular Disease in Patients with Rheumatoid ArthritisSoo-Kyung Cho (Hanyang Univ., Korea)

O-20-04 Comorbidities of Rheumatoid Arthritis: Results from

the 2010-2012 Korean National Health and Nutrition Examination SurveyHyemin Jeong (Samsung Medical Center, Korea)

O-20-05 Impacts of Disease Activity and Serum Level

of Brain-derived Neurotrophic Factor on Depression in Patients with Rheumatoid Arthritis Yun Hong Cheon (Gyeongsang National Univ., Korea)

09:50-10:30 Plenary Session II - International Free Paper Session (E) Chairs: Sang Cheol Bae (Hanyang Univ., Korea)

Seung-Cheol Shim (Chungnam National Univ., Korea)

O-20-06 Does Rheumatoid Arthritis Affect Bisphosphonate-related

Atypical Femur Fracture? Jung Hee Koh (The Catholic Univ., Korea)

O-20-07 Targeting IL-23 Can Attenuate Progression

of Spinal Ankylosis in Ankylosing Spondylitis Bon San Koo (Konkuk Univ., Korea)

The 36th Korean College of Rheumatology

Annual Scientific Meeting and the 10th International Symposium

Vol. 23, Suppl. 1, May, 2016 (K): Korean Session (E): English Session

O-20-08 Impact of Dose Tapering of Tumour Necrosis

Factor-blockers on Radiographic Progression in the Ankylosing Spondylitis: A 4-year Prospective Follow up from Single-centre Cohort

Jun Won Park (Seoul National Univ., Korea)

O-20-09 Insulin Resistance is Associated with Digital Ulcer

in Patients with Systemic Sclerosis Eun-Kyoung Park (Pusan National Univ., Korea)

10:30-11:00 Coffee Break & Poster Viewing

11:00-12:30 Invited Lectures I (E) Chairs: Yeong-Wook Song (Seoul National Univ., Korea)Jae-Bum Jun (Hanyang Univ., Korea)

11:00-11:30 Treatment of Lupus Nephritis Bevra Hahn (UCLA School of Medicine, USA)

11:30-12:00 Mechanistic Role of ACPA in Treatment OutcomesWilliam Hewitt Robinson (Stanford Univ. School of Medicine, USA)

12:00-12:30 Hyperuricemia and Cardiovascular Disease RiskHyon K. Choi (Harvard Medical School, USA)

12:30-13:30 Luncheon Symposium and Lunch Break (E)Chair: Choongki Lee (Yeungnam Univ., Korea)

Tofacitinib, an Oral Janus Kinase Inhibitor, as Monotherapy or with Background Methotrexate, in Japanese Patients with Rheumatoid Arthritis: An Open-label, Long-term Extension Study

Hisashi Yamanaka (Tokyo Women’s Medical Univ., Japan)

Grand Ballroom 1

13:30-15:00 Issues in Clinic Session (K) Chairs: Soo-Kon Lee (CHA Univ., Korea)Sang-Heon Lee (Konkuk Univ., Korea)

13:30-13:50 Bisphosphonate and Hydroxychloroquine in Rheumatic Diseases 이창근 (울산의대)

13:50-14:20 Rheumatism as a Co-morbidity of Medication Related Osteonecrosis of the Jaws 권용대 (경희치대)

14:20-14:50 Screening for Hydroxychloroquine Retinopathy: Why and How?김상진 (성균관의대 안과학교실)

14:50-15:00 Q&A

15:00-15:30 Coffee Break

15:30-17:00 Healthcare Policy Symposium (K)Chairs: Jung-Yoon Choe (Catholic Univ. of Daegu, Korea)

Sung-Hwan Park (Catholic Univ., Korea)

15:30-16:00 2016년도 보건의료정책 방향과 과제 정통령 (보건복지부 보험급여과)

16:00-16:30 류마티스 및 근골격계 질환의 질병 부담과 질 평가 이은봉 (서울의대)

16:30-17:00 류마티스 관절염 질지표 개발과 적용 백한주 (가천의대)

17:00-17:30 젊은 연구자상 및 학술상 수상 및 수상자 강연

17:30-18:00 General Assembly

Grand Ballroom 2

13:30-14:10 REOPHARD Session (K) Chairs: Dae-Hyun Yoo (Hanyang Univ., Korea)Shin-Seok Lee (Chonnam National Univ., Korea)

13:30-13:40 REOPHARD의 연혁과 기준 데이터의 분석 전찬홍 (순천향의대)

13:40-13:50 1차 추적 관찰 데이터의 분석 강귀영 (가톨릭의대)

13:50-14:00 KORPAH Registry 데이터의 분석 최성재 (고려의대)

14:00-14:10 결체조직질환에 동반된 폐동맥고혈압의 악화인자와 그 결과 서미령 (가천의대)

14:10-15:00 Free Paper Session: Rheumatoid Arthritis Clinical Aspects I (K)Chairs: Won Tae Chung (Dong-A Univ., Korea)

Seong Wook Kang (Chungnam National Univ., Korea)

O-20-10 Baseline Profiles in Korean Patients with

Rheumatoid Arthritis When Initiating or Switching Biologic Agents: Results from the KOBIO Registry Dong-Jin Park (Chonnam National Univ., Korea)

O-20-11 Drug Survival of Biologic Agents in Rheumatoid Arthritis

Using 10 Years of Nationwide Data in Korea: A Population-based StudyJeong Seok Lee (Seoul National Univ., Korea)

O-20-12 Efficacy and Safety of Add-on Treatment of Tacrolimus

Versus Leflunomide in Rheumatoid Arthritis Patients with Inadequate Response to Methotrexate Kichul Shin (SMG-SNU Boramae Medical Center, Korea)

O-20-13 The Impact of Korean Red Ginseng on Disease Activity and

Improvement of Fatigue in Patients with Rheumatoid Arthritis: A Randomized, Double-blind, Crossover Study Soo-Kyung Cho (Hanyang Univ., Korea)

O-20-14 Remission of Rheumatoid Arthritis Judged by 2 Criteria

Sung Yeon Lee (Hallym Univ., Korea)

Terrace Hall

13:30-14:10 Free Paper Session: Systemic Lupus Erythematosus, Sjogren's Syndrome Basic Aspects (K) Chairs: Jun-ki Min (Catholic Univ., Korea)

Hye-Soon Lee (Hanyang Univ., Korea)

O-20-15 A Selective JAK1 Inhibitor, Filgotinib Ameliorates

Sjogren's Syndrome in Non Obese Diabetes Mice Via Suppression of BAFF and Chemokine Production of Salivary Gland Epithelial Cells

Jennifer Jooha Lee (The Catholic Univ., Korea)

O-20-16 Exosomes from Patients with Active Systemic

Lupus Erythematosus Induce a Strong Inflammatory ResponseJoo Youn Lee (Seoul National Univ., Korea)

O-20-17 Urinary Immunoglobulin Binding Protein-1 as a Biomarker

Related with Lupus Nephritis Activity Eun-Ju Lee (Asan Medical Center, Korea)

O-20-18 Fn14-Fc Suppresses Germinal Center Formation

and Pathogenic B Cells in a Lupus Mouse Model via Inhibition of the TWEAK/Fn14 Pathway Hong Ki Min (The Catholic Univ., Korea)

14:10-15:00 Free Paper Session: Osteoarthritis (K) Chairs: Gun-Il Im (Dongguk Univ., Korea)Sung Won Lee (Dong-A Univ., Korea)

O-20-19 DICAM Promote Proliferation and Hypertrophic Differentiation

of Chondrocyte Through Indian Hedgehog Signaling of Primary CiliaSeung-Woo Han (Daegu Fatima Hosp., Korea)

O-20-20 Fibronectin Fragment Suppresses Xylosyltransferase-1

Expression Through Modulating Sp1 and Sp3 Expression Via MAPK, AP-1, and NF-κB Signaling Pathways Mi-Hyun Lee (Hallym Univ., Korea)

O-20-21 Metabolic and Inflammatory Links to Rotator Cuff Tear

in Hand Osteoarthritis Young Sun Suh (Gyeongsang National Univ., Korea)

O-20-22 Association between Grip Strength and Hand and

Knee Radiographic Osteoarthritis in Older Adults: Data from the Dong-gu StudyLihui Wen (Chonnam National Univ., Korea)

O-20-23 The Prevalence and Risk Factor of Knee Pain

in Advacned Knee Osteoarthritis Kyeong Min Son (Hallym Univ., Korea)

15:00-15:30 Coffee Break

15:30-16:10 Free Paper Session: Spondylarthropathies, Epidemiology (K)Chairs: Hyung In Yang (Kyung Hee Univ., Korea)

Young-Il Seo (Hallym Univ., Korea)

O-20-24 The Incidence of Herpes Zoster Infection in Patients

with Ankylosing Spondylitis: Analysis from Korean National Health Insurance Service-Cohort Sample Database Doo-Ho Lim (Univ. of Ulsan, Korea)

O-20-25 Utilization of the PEST Questionnaire to Detect

Psoriatic Arthritis in Clinical Practice: Data from the VALidation of psORiatic Arthritis Screening Tool for Korean Psoriasis Patients (VALOR) Study

You-Jung Ha (Seoul National Univ. Bundang Hosp., Korea)

O-20-26 Increased 18F-fluoride Uptake Lesions at Vertebral

Corners on Positron Emission Tomography Predict New Syndesmophytes Development in Ankylosing Spondylitis

Seung-Geun Lee (Pusan National Univ., Korea)

O-20-27 Korean Rheumatology Workforce from 1992 to 2015:

Rapid Advance, being on the Rise of Regional Concentration, in MetropolitanChan Uk Lee (Catholic Univ. of Daegu, Korea)

16:10-16:50 Free Paper Session: Behcet's Disease, Myositis (K)Chairs: Jinseok Kim (Jeju National Univ., Korea)

Yun-Jong Lee (Seoul National Univ., Korea)

O-20-28 Serum CXCL10 Levels are Associated with

Clinical Manifestations and Disease Activity in Behçet's Disease: A Prospective Follow-up Study Sang Jin Lee (Seoul National Univ., Korea)

O-20-29 Optimal Surgical Method for Aortic Regurgitation

in Behcet Disease Byeongzu Ghang (Univ. of Ulsan, Korea)

O-20-30 Major Comorbidities of Idiopathic Inflammatory Myositis

Affecting Survival and Functional Impairment: A Population-based Study Using 11 Years of Follow-up from the National Health Insurance in Korea

Jeong Seok Lee (Seoul National Univ., Korea)

O-20-31 C-Reactive Protein to Albumin as a New Prognostic

Value and Clinical Significance in Patients with DermatomyositisJaehyung Hur (Seoul National Univ. Bundang Hosp., Korea)

May 21 (Sat), 2016

Grand Ballroom 1

08:30-09:30 Breakfast Symposium (K) Chair: Won Park (Inha Univ., Korea)

Seeking for the Right ‘Combination’ of Conventional DMARDs in Rheumatoid Arthritis: Options Beyond Triple Combination

Kichul Shin (SMG-SNU Boramae Medical Center)

09:30-10:20 류마티스학 연구재단 연구과제 결과 보고 (K) Chairs: Gwan Gyu Song (Korea Univ., Korea)Jung-Soo Song (Chung-Ang Univ., Korea)

09:30-09:45 환자 교육이 류마티스관절염 환자의 만족도에 미치는 영향 성윤경 (한양의대)

09:45-10:00 류마티스관절염환자 대상 교육용 앱개발과 환자교육중재가 약제순응도 및 치료결과에 미치는 효과 주지현 (가톨릭의대)

10:00-10:10 질환특이 역분화 줄기세포 유도 정승민 (연세의대)

10:10-10:20 류마티스질환에서 대상포진의 위험인자 류희정 (가천의대)

10:20-11:00 Special Lectures (K) Chairs: Young Mo Kang (Kyungpook National Univ., Korea)Chang-Hee Suh (Ajou Univ., Korea)

10:20-10:30 유도만능줄기세포의 연골세포 분화 및 Crispr/Cas9 유전자 가위 시스템의 확립 한승우 (대구파티마병원)

10:30-10:40 T Cell Receptor Stimulation with Microbeads 김진현 (충남의대)

10:40-10:50 Translational Research in Keio University, Japan 김 담 (한양의대)


11:20-12:50 Invited Lectures II (E) Chairs: Bin Yoo (Univ. of Ulsan, Korea)Hyun Ah Kim (Hallym Univ., Korea)

11:20-11:50 Engineering New Biologic Therapies for OsteoarthritisFarshid Guilak (Washington Univ. in St. Louis, USA)

11:50-12:20 Pulmonary Arterial Hypertension in Connective Tissue Diseases Janet Pope (Univ. of Western Ontario and St. Joseph's Health Care, London Ontario, Canada)

12:20-12:50 Ultrasound in Rheumatology: Getting Closer to the Holy Grail?George AW Bruyn (MC Groep Hosp., Lelystad, The Netherlands)

12:50-13:10 Excellence Awards for Oral and Poster Presentation

Grand Ballroom 2

09:30-10:20 Free Paper Session: Rheumatoid Arthritis Basic Aspects (K)Chairs: Wan-Uk Kim (Catholic Univ., Korea)

Yong-Beom Park (Yonsei Univ., Korea)

O-21-01 Regulation of Autophagic Flux Alters Interleukin-17A-induced

Migration and Proliferation of Fibroblast-like Synoviocytes from the Patients with Rheumatoid Arthritis Ji-Min Kim (Keimyung Univ., Korea)

O-21-02 Interleukin-32 Exacerbates Synovial Inflammation and

Bone Destruction Via the Suppression of Raf Kinase Inhibitory ProteinHae Sook Noh (Gyeongsang National Univ., Korea)

O-21-03 NFAT5 Promotes Macrophage Survival by Inducing Chemokine Ligand 2

Susanna Choi (The Catholic Univ., Korea)

O-21-04 Autophagy Contributes to Celecoxib-induced Cell Death in Rheumatoid

Arthritis Fibroblast-like Synoviocytes Jihye Bang (Keimyung Univ., Korea)

O-21-05 Robust Therapeutic Efficacy of Matrix Metalloproteinase-2

Cleavable fas-1-RGD Peptide Complex on Chronic Inflammatory ArthritisEon Jeong Nam (Kyungpook National Univ., Korea)

10:20-11:00 Free Paper Session: Rheumatoid Arthritis Clinical Aspects II (K)Chairs: Chan-Hee Lee (NHIC Ilsan Hosp., Korea)

Eun Young Lee (Seoul National Univ., Korea)

O-21-06 Disease Characteristics and Change of Arthritis Activity

According to Treatment in Hepatitis B Surface Antigen Positive Rheumatoid Arthritis Patients YeongHee Eun (Samsung Medical Center, Korea)

O-21-07 Correlations Between Rheumatoid Arthritis Activity Indices and

Factors Affecting Acute Phase Reactants in Patients with Rheumatoid ArthritisIn Ah Choi (Chungbuk National Univ., Korea)

O-21-08 Achievement of Imaging Remission among Patients

with Rheumatoid Arthritis in Clinical Remission and Their CharacteristicsJi-Young Choi (Kyung Hee Univ., Korea)

O-21-09 HAQ Score is an Independent Predictor of Sustained Remission in

Patients with Rheumatoid Arthritis Kyung-Eun Lee (Chonnam National Univ., Korea)


11:20-12:50 Research Society Session on Spondyloarthritis (K)

11:20-12:10 1부 - 강직성 척추염에서 TNF 길항제의 사용Chair: Tae-Hwan Kim (Hanyang Univ., Korea)

11:20-11:35 Drug Survival of Tumor Necrosis Factor α Inhibitors in Patients with Ankylosing Spondylitis in Korea 정혜민 (성균관의대)

11:35-11:50 Safety of Resuming Tumor Necrosis Factor Inhibitors in Ankylosing Spondylitis Patients Concomitant with the Treatment of Active Tuberculosis 김혜원 (연세의대)

11:50-12:05 Low Dose Etanercept Treatment for Maintenance of Clinical Remission in Ankylosing Spondylitis 박준원 (서울의대)

12:05-12:10 Q&A

12:10-12:50 2부 - 강직성 척추염 NEWs and Updates Chair: Han-Joo Baek (Gachon Unvi., Korea)

12:10-12:30 Clinical Update on Spondyloarthritis 이연아 (경희의대)

12:30-12:50 Basic Update on Spondyloarthritis 이상훈 (경희의대)

Terrace Hall

09:30-10:20 Free Paper Session: Systemic Lupus Erythematosus Clinical Aspects (K)Chairs: Eun Bong Lee (Seoul National Univ., Korea)

Chang Keun Lee (Univ. of Ulsan, Korea)

O-21-10 Effects of Risk Factors for Metabolic Syndrome and the Components

of Metabolic Syndrome on the Quality of Life of Patients with Systemic Lupus Erythematosus: A Structural Equation Modeling Approach

Jeong-Won Lee (Chonnam National Univ., Korea)

O-21-11 Factors Related to Blood Hydroxychloroquine Concentration in Patients

with Systemic Lupus Erythematosus Ji Yeon Lee (Catholic Univ., Korea)

O-21-12 Factors Influencing on Health-Related Quality of Life in Korean

Patients with Systemic Lupus Erythematosus Su-Jin Moon (The Catholic Univ., Korea)

O-21-13 Corticosteroids Dose after 6 Months of Induction Therapy is

Associated with Non-Renal Organ Damage in Patients with Lupus NephritisChan-Bum Choi (Hanyang Univ., Korea)

O-21-14 Improved Survival of Systemic Lupus Erythematosus Patients

with Rituximab Treatment Na Ri Kim (Kyungpook National Univ., Korea)

10:20-11:00 Free Paper Session: Osteoporosis, Gout, Cytokines (K)Chairs: Young-Ho Lee (Korea Univ., Korea)Chong-Hyeon Yoon (Catholic Univ., Korea)

O-21-15 Glucocorticoid Acts Differently on Vertebral and Hip Fractures

in Korean RA Patients Using National Healthcare Claims DatabaseDam Kim (Hanyang Univ., Korea)

O-21-16 Ebselen is a Potential Anti-Osteoporosis Agent by Suppressing

Receptor Activator of NF-kB Ligand-Induced Osteoclast Differentiation and LPS-Induced Inflammatory Bone Destruction

Changhoon Lee (Wonkwang Univ., Korea)

O-21-17 p62 is Responsible for Interleukin-1b Production at the Early

Phase Through Mitochondrial Apoptosis by Monosodium Urate CrystalsSeong-Kyu Kim (Catholic Univ. of Daegu, Korea)

O-21-18 SIRT-1 Regulates TGF-b Induced Dermal Fibroblast Migration Via

Modulation of Cyr61 Expression Eun-Jeong Kwon (Jeju National Univ., Korea)

•Date: May 20 (Fri)∼21 (Sat), 2016 •Venue: Nine Tree Convention Gwanghwamun, Seoul, Korea

CO NTENTS May 20 (Fri), 2016

Plenary Session I - International Free Paper Session (E)

O-20-01 Urinary Interleukin-6 as a Predictor of Radiographic Progression in Rheumatoid Arthritis: A 3-year Evaluation

Yune-Jung Park, Seung-Ah Yoo, Ga-Ram Kim, Chul-Soo Cho, Wan-Uk Kim ········ S3

O-20-02 Baseline Autoantibodies Preferentially Impact Abatacept Efficacy in Patients with RA Who are Biologic Naïve: 6-Month Results from a Real-World, International, Prospective Study

Rieke Alten, Hubert G Nüßlein, Mauro Galeazzi, Hanns-Martin Lorenz, Xavier Mariette, Alain Cantagrel, Melanie Chartier, Guillaume Desachy,

Coralie Poncet, Christine Rauch, Manuela Le Bars ········ S4

O-20-03 The Effect of Medication on Development of Cardiovascular Disease in Patients with Rheumatoid Arthritis

Soo-Kyung Cho, Dam Kim, Soyoung Won, Minkyung Han, Jiyoung Lee, Eun Jin Jang, Sang-Cheol Bae, Yoon-Kyoung Sung ········ S5

O-20-04 Comorbidities of Rheumatoid Arthritis: Results from the 2010-2012 Korean National Health and Nutrition Examination Survey

Hyemin Jeong, Sun Young Beak, Yeong Hee Eun, In Young Kim, Hyungjin Kim, Joong Kyong Ahn, Jaejoon Lee, Eun-Mi Koh, Hoon-Suk Cha ········ S6

O-20-05 Impacts of Disease Activity and Serum Level of Brain-derived Neurotrophic Factor on Depression in Patients with Rheumatoid Arthritis

Yun-Hong Cheon, Hyun-Ok Kim, Young Sun Suh, Sang-Hyon Kim, Ji-Min Kim, Chang-Nam Son, Seung-Geun Lee, Eun Kyoung Park, Sang-Il Lee ········ S7

Plenary Session II - International Free Paper Session (E)

O-20-06 Does Rheumatoid Arthritis Affect Bisphosphonate-related Atypical Femur Fracture? Jung Hee Koh, Jennifer Lee, Seung-Ki Kwok, Wan-Uk Kim, Sung-Hwan Park, Ji Hyeon Ju ····· S11

O-20-07 Targeting IL-23 Can Attenuate Progression of Spinal Ankylosis in Ankylosing Spondylitis

Sungsin Jo, Bon San Koo, Il-Hoon Sung, Ye-Soo Park, Tae-Hwan Kim ····· S12

The 36th Korean College of Rheumatology

Annual Scientific Meeting and the 10th International Symposium

Vol. 23, Suppl. 1, May, 2016 (K): Korean Session (E): English Session

O-20-08 Impact of Dose Tapering of Tumour Necrosis Factor-blockers on Radiographic Progression in the Ankylosing Spondylitis: A 4-year Prospective Follow Up from Single-centre Cohort

Jun Won Park, Hyun Mi Kwon, Jin Kyun Park, Ja-Young Choi, Eun Bong Lee, Yeong Wook Song, Eun Young Lee ····· S13

O-20-09 Insulin Resistance is Associated with Digital Ulcer in Patients with Systemic Sclerosis

Eun-Kyoung Park, Seung-Geun Lee, Ji-Heh Park ····· S14

Invited Lectures I (E)

1. Treatment of Lupus Nephritis Bevra Hahn ····· S17

2. Sequencing Antibody Repertoires to Decipher Pathogenic Mechanisms in Rheumatoid Arthritis William Hewitt Robinson ····· S25

3. Hyperuricemia and Cardiovascular Disease Risk Hyon K. Choi ····· S26

Luncheon Symposium and Lunch Break (E)

1. Tofacitinib, an Oral Janus Kinase Inhibitor, as Monotherapy or with Background Methotrexate, in Japanese Patients with Rheumatoid Arthritis: An Open-label, Long-term Extension Study Hisashi Yamanaka ····· S31

Issues in Clinic Session (K)

1. BP & HCQ Uses in Rheumatic Diseases 이창근 ····· S35

2. Rhuematism as a co-morbidity of Medication Related Osteonecrosis of the Jaws (MRONJ) 권용대 ····· S42

3. Screening for Hydroxychloroquine Retinopathy: Why and How? 김상진 ····· S43

Healthcare Policy Symposium (K)

1. 2016년 의료질 평가 정통령 ····· S49

2. 류마티스 및 근골격계 질환의 질병 부담 및 질관리 현황 이은봉 ····· S56

3. 류마티스관절염 질지표 개발과 적용 백한주 ····· S57

REOPHARD Session (K)

1. REOPHARD: History of the Registry and Analysis of Baseline Data 전찬홍 ····· S61

2. Survival and Prognostic Factors in Patients with Connective Tissue Disease-associated Pulmonary Hypertension by Echocardiography: Results from a Korean Nationwide Registry 강귀영 ····· S62

3. KORPAH Registry 데이터의 분석 최성재 ····· S63

4. Progression and Outcomes in Patients with Pulmonary Artery Hypertension Associated with Systemic Rheumatic Diseases: Results from a Korean Nationwide Registry 서미령 ····· S65

Free Paper Session: Rheumatoid Arthritis Clinical Aspects I (K)

O-20-10 Baseline Profiles in Korean Patients with Rheumatoid Arthritis when Initiating or Switching Biologic Agents: Results from the KOBIO Registry

Dong-Jin Park, Ji-Hyoun Kang, Yi-Rang Yim, Ji-Eun Kim, Jeong-Won Lee, Kyung-Eun Lee, Lihui Wen, Tae-Jong Kim, Yong-Wook Park, Shin-Seok Lee ····· S69

O-20-11 Drug Survival of Biologic Agents in Rheumatoid Arthritis Using 10 Years of Nationwide Data in Korea: A Population-based Study

Jeong Seok Lee, Jun Won Park, Eunyoung Emily Lee, Yeong Wook Song, Hee Young Lee, Eun Young Lee ····· S70

O-20-12 Efficacy and Safety of Add-on Treatment of Tacrolimus versus Leflunomide in Rheumatoid Arthritis Patients with Inadequate Response to Methotrexate

Kichul Shin, Han Joo Baek, Young Mo Kang, Hoon-Suk Cha, Seong Wook Kang, Sung-Hwan Park, Jae Bum Jun,

Yun Jong Lee, Yeong Wook Song ····· S71

O-20-13 The Impact of Korean Red Ginseng on Disease Activity and Improvement of Fatigue in Patients with Rheumatoid Arthritis: A Randomized, Double-blind, Crossover Study

Soo-Kyung Cho, DasomiYoo, Dam Kim, Yoon-Kyoung Sung ····· S72

O-20-14 Remission of Rheumatoid Arthritis Judged by 2 CriteriaSung Yeon Lee, Kyeong Min Son, Young Il Seo, Hyun Ah Kim ····· S73

Free Paper Session: Systemic Lupus Erythematosus, Sjogren's Syndrome Basic Aspects (K)

O-20-15 A Selective JAK1 Inhibitor, Filgotinib Ameliorates Sjogren's Syndrome in Non Obese Diabetes Mice Via Suppression of BAFF and Chemokine Production of Salivary Gland Epithelial Cells

Jennifer Lee, Jaeseon Lee, Seung-Ye Baek, Seung-Ki Kwok, Mi-La Cho, Sung-Hwan Park ····· S77

O-20-16 Exosomes from Patients with Active Systemic Lupus Erythematosus Induce a Strong Inflammatory Response

Joo Youn Lee, Jin Kyun Park, Eun Young Lee, Eun Bong Lee, Yeong Wook Song ····· S78

O-20-17 Urinary Immunoglobulin Binding Protein-1 as a Biomarker Related with Lupus Nephritis Activity

Eun-Ju Lee, Seokchan Hong, Bin Yoo, Chang-Keun Lee, Yong-Gil Kim ····· S79

O-20-18 Fn14-Fc Suppresses Germinal Center Formation and Pathogenic B Cells in a Lupus Mouse Model Via Inhibition of the TWEAK/Fn14 Pathway

Hong-Ki Min, Sung-Min Kim, Jin-Sil Park, Jae-Kyeong Byun, Jennifer Lee, Seung-Ki Kwok, Young-Woo Park, Mi-La Cho, Sung-Hwan Park ····· S80

Free Paper Session: Osteoarthritis (K)

O-20-19 DICAM Promote Proliferation and Hypertrophic Differentiation of Chondrocyte through Indian Hedgehog Signaling of Primary Cilia

Seung-woo Han, Min-Su Han, Hye-Ri Park, Eun-Ju Lee, Ji-Ae Jang, Gun-Woo Kim, Youn-Kwan Jung ····· S83

O-20-20 Fibronectin Fragment Suppresses Xylosyltransferase-1 Expression through Modulating Sp1 and Sp3 Expression Via MAPK, AP-1, and NF-κB Signaling Pathways

Mi Hyun Lee, Hyun Sook Hwang, Hyun Ah Kim ····· S84

O-20-21 Metabolic and Inflammatory Links to Rotator Cuff Tear in Hand OsteoarthritisYoung Sun Suh, Yun-Hong Cheon, Hyun-Ok Kim, Rock-Bum Kim,

Ki Soo Park, Hyung Bin Park, Jae-Bum Na, Sang-Il Lee ····· S85

O-20-22 Association between Grip Strength and Hand and Knee Radiographic Osteoarthritis in Older Adults: Data from the Dong-gu Study

Lihui Wen, Ji-Hyoun Kang, Yi-Rang Yim, Ji-Eun Kim, Jeong-Won Lee, Kyung-Eun Lee, Dong-Jin Park, Tae-Jong Kim,

Yong-Wook Park, Sun-Seog Kweon, Young-Hoon Lee, Yong-Woon Yun, Min-Ho Shin, Shin-Seok Lee ····· S86

O-20-23 The Prevalence and Risk Factor of Knee Pain in Advacned Knee OsteoarthritisKyeong Min Son, Dong-Hyun Kim,

MyungHee Cho Paik, Dae Gyu Jang, Hyun Ah Kim ····· S87

Free Paper Session: Spondylarthropathies, Epidemiology (K)

O-20-24 The Incidence of Herpes Zoster Infection in Patients with Ankylosing Spondylitis: Analysis from Korean National Health Insurance Service-Cohort Sample Database

Doo-Ho Lim, Byeongzu Ghang, Seokchan Hong, Yong-Gil Kim, Chang-Keun Lee, Bin Yoo ····· S91

O-20-25 Utilization of the PEST Questionnaire to Detect Psoriatic Arthritis in Clinical Practice: Data from the VALidation of psORiatic Arthritis Screening Tool for Korean Psoriasis Patients (VALOR) Study

You-Jung Ha, So Yeon Cho, Sang-Heon Lee, Yong Beom Choe, Tae-Hwan Kim, Joo Yeon Ko, Sung Jae Choi, Il-Hwan Kim, Sang Woong Youn, Kichul Shin ····· S92

O-20-26 Increased 18F-fluoride Uptake Lesions at Vertebral Corners on Positron Emission Tomography Predict New Syndesmophytes Development in Ankylosing Spondylitis

Seung-Geun Lee, Eun-Kyoung Park, Ji-Heh Park ····· S93

O-20-27 Korean Rheumatology Workforce from 1992 to 2015: Rapid Advance, being on the Rise of Regional Concentration, in Metropolitan

Chan Uk Lee, Sung-Hoon Park, Hwajeong Lee, Ji-Na Kim, Ji-Won Kim, Seong-Kyu Kim, Jung-Yoon Choe ····· S94

Free Paper Session: Behcet's Disease, Myositis (K)

O-20-28 Serum CXCL10 Levels are Associated with Clinical Manifestations and Disease Activity in Behçet’s Disease: A Prospective Follow-up Study

Sang Jin Lee, Eun Ha Kang, Byoong Yong Choi, Shin Eui Kang, Jin Kyun Park, Eun Young Lee, Eun Bong Lee, Yeong Wook Song ····· S97

O-20-29 Optimal Surgical Method for Aortic Regurgitation in Behcet DiseaseByeongzu Ghang, Suk Jung Choo, Ohchan Kwon, Wook Jang Seo,

Seokchan Hong, Yong-Gil Kim, Chang-Keun Lee, Bin Yoo ····· S98

O-20-30 Major Comorbidities of Idiopathic Inflammatory Myositis Affecting Survival and Functional Impairment: A Population-based Study Using 11 Years of Follow Up from the National Health Insurance in Korea

Jeong Seok Lee, Min Jung Kim, Hee Young Lee, So Yeon Ahn, Yeong Wook Song, Eun Bong Lee,

Eun Young Lee, Yun Jong Lee, Eun Ha Kang ····· S99

O-20-31 C-Reactive Protein to Albumin as a New Prognostic Value and Clinical Significance in Patients with Dermatomyositis

Jaehyung Hur, Dong Jin Go, Sang Wan Chung, You-Jung Ha, Eun Ha Kang, Jin Kyun Park, Kichul Shin, Eun Young Lee,

Eun Bong Lee, Yeong Wook Song, Yun Jong Lee ··· S100

May 21 (Sat), 2016

Breakfast Symposium (K)

1. Seeking for the Right ‘Combination’ of Conventional DMARDs in Rheumatoid Arthritis: Options Beyond Triple Combination Kichul Shin ··· S103

류마티스학 연구재단 연구과제 결과 보고 (K)

1. Impact of Patient Education on Outcomes in RA Patients 성윤경 ··· S107

2. 류마티스관절염환자 대상 교육용 앱개발과 환자교육중재가 약제순응도 및 치료결과에 미치는 효과 주지현 ··· S112

3. 질환특이 역분화 줄기세포 유도 정승민 ··· S113

4. Risk Factors of Herpes Zoster in Patients with Rheumatic Diseases in Korea 류희정 ··· S114

Special Lectures (K)

1. 유도만능줄기세포의 연골세포 분화 및 Crispr/Cas9 유전자 가위 시스템의 확립 한승우 ··· S117

2. T Cell Receptor Stimulation with Microbeads 김진현 ··· S118

3. Change of Regulatory T Cells in RA Patients with Tocilizumab 김 담 ··· S119

Invited Lectures II (E)

1. Engineering New Biologic Therapies for Osteoarthritis Farshid Guilak ··· S123

2. Pulmonary Arterial Hypertension in the Connective Tissue Diseases Janet Pope ··· S124

3. Ultrasound in Rheumatology: Getting Closer to the Holy Grail? George AW Bruyn ··· S126

Free Paper Session: Rheumatoid Arthritis Basic Aspects (K)

O-21-01 Regulation of Autophagic Flux Alters Interleukin-17A-induced Migration and Proliferation of Fibroblast-like Synoviocytes from the Patients with Rheumatoid Arthritis

Ji-Min Kim, Jihye Bang, Hye-Jin Jeong, Chang-Nam Son, Sang-Hyon Kim ··· S131

O-21-02 Interleukin-32 Exacerbates Synovial Inflammation and Bone Destruction Via the Suppression of Raf Kinase Inhibitory Protein

Hae Sook Noh, Hye Song Lim, Sang Mi Yi, Min-Gyu Jeon, Beow Yong Park, Hee Young Cho, Young-Sool Hah, Yun-Hong Cheon, Sang-Il Lee ··· S132

O-21-03 NFAT5 Promotes Macrophage Survival by Inducing Chemokine Ligand 2Susanna Choi, Sungyong Yoo, Soo Youn Choi, H. Moo Kwon, Hyun-Sook Kim, Daehee Hwang, Chul-Soo Cho, Wan-Uk Kim ··· S133

O-21-04 Autophagy Contributes to Celecoxib-induced Cell Death in Rheumatoid Arthritis Fibroblast-like Synoviocytes

Jihye Bang, Hye-Jin Jeong, Chang-Nam Son, Ji-Min Kim, Sang-Hyon Kim ··· S134

O-21-05 Robust Therapeutic Efficacy of Matrix Metalloproteinase-2 Cleavable fas-1-RGD Peptide Complex on Chronic Inflammatory Arthritis

Eon Jeong Nam, Jin Hee Kang, Keum Hee Sa, Shijin Sung, Jeong Soo Eun, Na Ri Kim, Young Mo Kang ··· S135

Free Paper Session: Rheumatoid Arthritis Clinical Aspects II (K)

O-21-06 Disease Characteristics and Change of Arthritis Activity According to Treatment in Hepatitis B Surface Antigen Positive Rheumatoid Arthritis Patients

YeongHee Eun, In Young Kim, Hyemin Jeong, Hyungjin Kim, Jaejoon Lee, Eun-Mi Koh, Hoon-Suk Cha ··· S139

O-21-07 Correlations between Rheumatoid Arthritis Activity Indices and Factors Affecting Acute Phase Reactants in Patients with Rheumatoid Arthritis

In Ah Choi ··· S140

O-21-08 Achievement of Imaging Remission among Patients with Rheumatoid Arthritis in Clinical Remission and Their Characteristics

Ji-Young Choi, Seung-Jae Hong, Hyung-In Yang, Sang-Hoon Lee, Ran Song, Yeon-Ah Lee ··· S141

O-21-09 HAQ Score is an Independent Predictor of Sustained Remission in Patients with Rheumatoid Arthritis

Kyung-Eun Lee, Ji-Hyoun Kang, Yi-Rang Yim, Ji-Eun Kim, Jeong-Won Lee, Lihui Wen, Dong-Jin Park, Tae-Jong Kim, Yong-Wook Park, Shin-Seok Lee ··· S142

Research Society Session on Spondyloarthritis (K) 1부 - 강직성 척추염에서 TNF 길항제의 사용

1. Drug Survival of Tumor Necrosis Factor α Inhibitors in Patients with Ankylosing Spondylitis in Korea 정혜민 ··· S145

2. Safety of Resuming Tumor Necrosis Factor Inhibitors in Ankylosing Spondylitis Patients Concomitant with the Treatment of Active Tuberculosis: A Retrospective Nationwide Registry of the Korean Society of Spondyloarthritis Research 김혜원 ··· S146

3. Low Dose Etanercept Treatment for Maintenance of Clinical Remission in Ankylosing Spondylitis 박준원 ··· S147

Research Society Session on Spondyloarthritis (K) 2부 - 강직성 척추염 NEWs and Updates

1. Clinical Update on Spondyloarthritis 이연아 ··· S151

2. 척추관절염 Update: Basic and Translational Research 이상훈 ··· S158

Free Paper Session: Systemic Lupus Erythematosus Clinical Aspects (K)

O-21-10 Effects of Risk Factors for Metabolic Syndrome and the Components of Metabolic Syndrome on the Quality of Life of Patients with Systemic Lupus Erythematosus: A Structural Equation Modeling Approach

Jeong-Won Lee, Ji-Hyoun Kang, Yi-Rang Yim, Ji-Eun Kim, Kyung-Eun Lee, Lihui Wen, Dong-Jin Park, Tae-Jong Kim, Yong-Wook Park, Shin-Seok Lee ··· S165

O-21-11 Factors Related to Blood Hydroxychloroquine Concentration in Patients with Systemic Lupus Erythematosus

Ji Yeon Lee, Seung Ki Kwok, Ji Hyeon Ju, Kyung Su Park, Sung-Hwan Park ··· S166

O-21-12 Factors Influencing on Health-Related Quality of Life in Korean Patients with Systemic Lupus Erythematosus

Su-Jin Moon, Kwi Young Kang, Seung-Ki Kwok, Ji Hyeon Ju, Wan-Uk Kim, Yeon-Sik Hong, Sung-Hwan Park, Chan Hong Jeon,

Sang Tae Choi, Jung-Soo Song, Jun-Ki Min ··· S167

O-21-13 Corticosteroids Dose After 6 Months of Induction Therapy is Associated with Non-Renal Organ Damage in Patients with Lupus Nephritis

Chan-Bum Choi, Young Bin Joo, Soyoung Won, Sang-Cheol Bae ··· S168

O-21-14 Improved Survival of Systemic Lupus Erythematosus Patients with Rituximab Treatment

Na Ri Kim, Jung Su Eun, Jong Wan Kang, Eon Jeong Nam, Young Mo Kang ··· S169

Free Paper Session: Osteoporosis, Gout, Cytokines (K)

O-21-15 Glucocorticoid Acts Differently on Vertebral and Hip Fractures in Korean RA Patients Using National Healthcare Claims Database

Dam Kim, Soo-Kyung Cho, Byeongju Park, Eun Jin Jang, Sang-Cheol Bae, Yoon-Kyoung Sung ··· S173

O-21-16 Ebselen is a Potential Anti-Osteoporosis Agent by Suppressing Receptor Activator of NF-κB Ligand-Induced Osteoclast Differentiation and LPS-Induced Inflammatory Bone Destruction

Changhoon Lee, Jong Min Baek, Ju-Young Kim, Jaemin Oh, Myeung-Su Lee ··· S174

O-21-17 p62 is Responsible for Interleukin-1β Production at the Early Phase through Mitochondrial Apoptosis by Monosodium Urate Crystals

Seong-Kyu Kim, Jung-Yoon Choe, Ji Na Kim, Ji-Won Kim, Chan Uk Lee ··· S175

O-21-18 SIRT-1 Regulates TGF-β Induced Dermal Fibroblast Migration Via Modulation of Cyr61 Expression

Eun-Jeong Kwon, Eun-Jung Park, Moonjae Cho, Jinseok Kim ··· S176

Poster Presentation

1. The Synovial Fluid Concentrations of Cold-inducible RNA-binding Protein are Correlated with Disease Activity in Patients with Rheumatoid Arthritis

In Seol Yoo, Young Kim, Seong Wook Kang, Seung-Cheol Shim, Jinhyun Kim, Su-Jin Yoo, Sun Young Lee, Chan Keol Park ··· S179

2. A Role of Synovial Exosomes in Osteoclast Differentiation of Inflammatory ArthritisJi Eun Song, Ji Hye Shin, Ki Won Moon, Se Hui Shon, Ji Soo Park,

Eun Bong Lee, Yeong Wook Song, Eun Young Lee ··· S180

3. The Relationship between the Articular Surface Projection and Radiologic Laxity of the Trapeziometacarpal Joint

Jeong Hwan Kim, Hyun Sik Gong, Jihyeung Kim, Goo Hyun Baek ··· S181

4. Impact of Myofascial Pain Syndrome on Pain and Functional Status in Patients with Hand Osteoarthritis

Young Sun Suh, Yun-Hong Cheon, Hyun-Ok Kim, Rock-Bum Kim, Ki Soo Park, Hyung Bin Park, Jae-Bum Na, Sang-Il Lee ··· S182

5. The Value of High-sensitivity C-reactive Protein in Hand and Knee Radiographic Osteoarthritis: Data from the Dong-gu Study

Yi-Rang Yim, Lihui Wen, Ji-Hyoun Kang, Ji-Eun Kim, Jeong-Won Lee, Kyung-Eun Lee, Dong-Jin Park, Tae-Jong Kim, Yong-Wook Park, Sun-Seog Kweon,

Young-Hoon Lee, Yong-Woon Yun, Min-Ho Shin, Shin-Seok Lee ··· S183

6. Leptin Protects Rat Articular Chondrocytes from TNF-α Cytotoxicity Induced by Cyclohexamide

Sang Yeob Lee, Sung Won Lee, Won Tae Chung ··· S184

7. Association-heterogeneity Mapping Identifies an Asian-specific Association of the GTF2I Locus with Rheumatoid Arthritis

Kwangwoo Kim, So-Young Bang, Katsunori Ikari, Dae Hyun Yoo, Soo-Kyung Cho, Chan-Bum Choi, Yoon-Kyoung Sung, Tae-Hwan Kim, Jae-Bum Jun, Young Mo Kang,

Chang-Hee Suh, Seung-Cheol Shim, Shin-Seok Lee, Jisoo Lee, Won Tae Chung, Seong-Kyu Kim, Jung-Yoon Choe, Shigeki Momohara, Atsuo Taniguchi,

Hisashi Yamanaka, Swapan K Nath, Hye-Soon Lee, Sang-Cheol Bae ··· S185

8. Stauntonia Hexaphylla Extract Suppresses Expression of Pro-inflammatory Mediators, MMPs through Downregulating Akt, p38, JNK and NF-κB Activation in Rheumatoid Arthritis Fibroblast-like Synoviocytes

Hyung Jung Yoo, Jeong Yeon Kim, Shin Eui Kang, Ji Soo Park, Eun Young Lee, Eun Bong Lee, Yeong Wook Song ··· S186

9. Hypoxia Induce Slug Expression Via JAK/STAT3 Pathway in Rheumatoid Arthritis Fibroblast-like Synoviocytes

Hyungjin Kim, Hyemin Jeong, Jaejoon Lee, Hoon-Suk Cha, Eun-Mi Koh, Joong Kyong Ahn ··· S187

10. Pioneering Study about Expression of Programmed Death-1 (PD-1) with Its Ligands on Synoviocyte, Macrophage and Lymhpocyte in Synovial Fluid of Rheumatoid Arthritis

Sang Yeob Lee, Sung Won Lee, Won Tae Chung, Jae Ho Bae ··· S188

11. The Jak-2 Mutation in Rheumatoid Arthritis PathogenesisTaskin Senturk, Ikbal Akdam, Irfan Yavasoglu, Gohan Bozkurt ··· S189

12. Identification of Differential Expressions of NOD-like Receptors and Their Signaling Pathway in Rheumatoid FLS and Synovium

Ji-Yoen Moon, Byung Wook Park, Yong-Jin Kwon, Hye Won Kim, Min-Chan Park ··· S190

13. Histamine and Histamine H4 Receptor Promotes Osteoclastogenesis in Rheumatoid ArthritisHae-Rim Kim, Kyung-Ann Lee, Kyoung-Woon Kim, Bo-Mi Kim, Sang-Heon Lee ··· S191

14. Rheumatoid Arthritis is Associated with Low/mid Frequency Hearing Impairment: Results from the 2010-2012 Korean National Health and Nutrition Examination Survey

Hyemin Jeong, Young-Soo Chang, Sun Young Baek, Sun Woo Kim, Yeong Hee Eun, In Young Kim, Jaejoon Lee, Eun-Mi Koh, Hoon-Suk Cha ··· S192

15. High Fat Mass Predicts the Persistence/Progression of Musculoskeletal Pain in Community Residents

Hyun-Ah Kim, Seung Hun Lim, Nam Han Cho ··· S193

16. Biological Function Enriched Prediction of Severe Radiographic Progression in Rheumatoid Arthritis

Young Bin Joo, Yul Kim, Youngho Park, Kwangwoo Kim, Jeong Ah Ryu, Seunghun Lee, So-Young Bang, Hye-Soon Lee, Gwan-Su Yi, Sang-Cheol Bae ··· S194

17. A Korean Multicenter Observational Study of Disease Activity Changes in BIologic versus Non-biologic Users with Seropositive Rheumatoid Arthritis

Kichul Shin, Sung Soo Kim, Sang Heon Lee, Seung Jae Hong, Sung Jae Choi, Jung yoon Choe, Seung- Geun Lee, Hoon-Suk Cha, Eun Young Lee, Sung-Hwan Park,

Jin Wuk Hur, Sung Soo Na, Chang Hee Suh, So Min Wook, Seung Won Choi, Dong Hyuk Sheen, Won Park, Shin-Seok Lee, Myong Joo Hong, Jin Seok Kim,

Jung Soo Song, Hye Soon Lee, Seong Ho Kim, Dae-Hyun Yoo ··· S195

18. Seropositivity and Its Impact on Radiographic Damage in Korean Rheumatoid Arthritis Patients Starting Biologics

Kichul Shin, Seungjun Ha, Inkyung Jung, Hyoun-Ah Kim, Shin-Seok Lee ··· S196

19. Achievement of Imaging Remission among Patients with Rheumatoid Arthritis in Clinical Remission and Their Characteristics


20. Achievement of Imaging Remission among Patients with Rheumatoid Arthritis in Clinical Remission and Their Characteristics


21. Assessment of Liver Fibrosis Using Transient Elastography in Patients with Rheumatoid Arthritis Exposed to Long Term Methotrexate

Min Kyung Chung, Jung Hee Koh, Jennifer Lee, Seung-Ki Kwok, Ji Hyeon Ju, Sung-Hwan Park ··· S199

22. The Effect of TNF Blockers on Bone Mineral Density in Rheumatoid Arthritis Patients Receiving Bisphosphonate

Doo-Ho Lim, Byeongzu Ghang, Seokchan Hong, Yong-Gil Kim, Chang-Keun Lee, Bin Yoo ··· S200

23. A Rare Case of Branch Retinal Vein Occlusion Complicating Rheumatoid ArthritisMi-Hye Kwon, Younghoon Lee, Chung-Il Joung ··· S201

24. On Drug and Drug-Free Remission by Baseline Disease Duration: Abatacept Versus Methotrexate Comparison in Patients with Early Rheumatoid Arthritis

Vivian P. Bykerk, Gerd R. Burmester, Bernard G. Combe, Daniel E. Furst, Tom W.J. Huizinga, Dennis A. Wong, Paul Emery ··· S202

25. Abatacept Plus Methotrexate Can Effectively and Safely Regain the Target of Remission Following Re-treatment for Flares after Drug-Free Withdrawal in Patients with Early Rheumatoid Arthritis

Paul Emery, Gerd R. Burmester, Vivian P. Bykerk, Bernard G. Combe, Daniel E. Furst, Michael Maldonado, Thomas W. Huizinga ··· S203

26. Factors Associated with Hydroxychroloquine Retinal ToxicityJi-Won Kim, Chan Uk Lee, Ji-Na Kim, Se Eun Kim, Yun Young Kim,

Hwajeong Lee, Sung-Hoon Park, Seong-Kyu Kim, Jung-Yoon Choe ··· S204

27. Improvement of Morning Stiffness in Korean Rheumatoid Arthritis Patients after Treatment with a New Modified-release form of Prednisone

Kichul Shin, Sung-Soo Kim, Sung Jae Choi, Geun-Tae Kim, Sang-Hyon Kim, Myeong Soo Lee, Jin-Wuk Hur, Yun Sung Kim, Young Il Seo, Seong-Su Nah,

Hyun-Sook Kim, Eun Young Lee, Seung-Jae Hong ··· S205

WithdrawWithdrawWithdraw

WithdrawWithdrawWithdraw

28. Withdrawal of Nonsteroidal Anti-inflammatory Drugs in Rheumatoid Arthritis Patients with Low Disease Activity

Dong Jin Go, Kichul Shin, Han Joo Baek, Seong Wook Kang, Young Mo Kang, Jae Bum Jun, Yun Jong Lee, Sung Hwan Park, Yeong Wook Song ··· S206

29. Varicella-zoster Virus Specific Cell-mediated Immunity is Decreased in Patients with Rheumatoid Arthritis Receiving Varicella Vaccine

Jung-Hee Koh, Jennifer Lee, Seung-Ki Kwok, Ji Hyeon Ju, Wan-Uk Kim, Sung-Hwan Park ··· S207

30. Body Mass Index Does Not Influence the Efficacy of Abatacept in Patients with RA Who are Biologic-DMARD Naïve: 6-Month Results from a Real-World, International, Prospective Study

Rieke Alten, Hubert G Nüßlein, Mauro Galeazzi, Hanns-Martin Lorenz, Xavier Mariette, Alain Cantagrel, Melanie Chartier, Guillaume Desachy,

Coralie Poncet, Christine Rauch, Manuela Le Bars ··· S208

31. Safety of Biologics in Patients with Rheumatoid Arthritis and Hepatitis C Virus Infection: A Multicenter Retrospective Study

Hyun Mi Kwon, Kichul Shin, Shin-Seok Lee, Won Tae Chung, Jisoo Lee, Sang-Heon Lee, Seong-Wook Kang, Chang Hee Suh, Seung-Jae Hong,

Ran Song, Jung-Yoon Choe, Yeong Wook Song ··· S209

32. Baricitinib Versus Placebo or Adalimumab in Patients with Active Rheumatoid Arthritis and an Inadequate Response to Background Methotrexate Therapy: Results of a Phase 3 Study

Jieon Won, Peter C. Taylor, Edward C. Keystone, Désirée van der Heijde, Yoshiya Tanaka, Taeko Ishii, Kahaku Emoto, Lili Yang, Vipin Arora,

Carol Gaich, Terence Rooney, Douglas Schlichting, William L. Macias, Stephanie de Bono, Michael E. Weinblatt ··· S210

33. Evaluation of the Relationship between IL-10, IL-17, IL-23 Levels and Disease Activity of Systemic Lupus Erythematosus and Vitamin D Metabolism

Taskin Senturk, Beyza Cetin, Gokhan Sargin, Neriman Aydin ··· S211

34. Comparison of the Clinical, Serological, and Prognostic Differences among Juvenile-, Adult-, and Late-onset Lupus Nephritis in Korean Patients: A Case-control Study

Ji-Hyoun Kang, Dong-Jin Park, Yi-Rang Yim, Ji-Eun Kim, Jeong-Won Lee, Kyung-Eun Lee, Lihui Wen, Tae-Jong Kim, Yong-Wook Park, Shin-Seok Lee ··· S212

35. Body Mass Index, HDL Cholesterol, Taking NSAID, and Current Dose of Glucocorticoids Might Contribute to Subclinical Atherosclerosis in SLE Patients with Low Disease Activity

Ju-Yang Jung, Hyun-Ah Kim, Chang-Hee Suh ··· S213

36. Antiphospholipid Antibody Positivity and Related Clinical Characteristics in Korean Lupus Patients

Dam Kim, Soo-Kyung Cho, Kyung-Eun Lee, Dong-Jin Park, Shin-Seok Lee, Yoon-Kyoung Sung ··· S214

37. Lupus Nephritis is Associated with more Corticosteroid-associated Organ Damage but Less Corticosteroid Non-associated Organ Damage

Young Bin Joo, Soyoung Won, Chan-Bum Choi, Sang-Cheol Bae ··· S215

38. Comparison of Clinical and Serological Differences According to the Autoantibody Cluster in Women with Systemic Lupus Erythematosus: Results from the Korean Lupus Network (KORNET) Registry

Ji-Eun Kim, Dong-Jin Park, Ji-Hyoun Kang, Yi-Rang Yim, Jeong-Won Lee, Kyung-Eun Lee, Lihui Wen, Tae-Jong Kim, Yong-Wook Park, Shin-Seok Lee ··· S216

39. Vitamin D and Bone Mineral Density in Rheumatoid Arthritis and Systemic Lupus Erythematosus

Ju-Yang Jung, Hyoun-Ah Kim, Chang-Hee Suh ··· S217

40. Salivary Proteomic Analysis in the Patients with Systemic Lupus Erythematosus Ju-Yang Jung, Hyun-Ah Kim, Jin-Young Nam and Chang-Hee Suh ··· S218

41. The Increase or Decrease of Serially Assessed anti ds-DNA Antibody Serum Level is Strong Relationship with Lupus Flare Up: Single Center Experience

Sang Yeob Lee, Sung Won Lee, Won Tae Chung ··· S219

42. Outcomes in Patients with Ischemic Stroke Regarding Titer and Persistence of Antiphospholipid Antibodies

Jung Yoon Pyo, Sang-Won Lee, Jason Jungsik Song, Yong-Beom Park ··· S220

43. Cytomegalovirus Reactivation in Patient with Active Lupus Nephritis Hyunae Lee, yeunmi Kang, Jihyun Han, Sangyoon Kim, In Je Kim, Jisoo Lee ··· S221

44. A Case of Systemic Lupus Erythematosus Presenting as Stevens-Johnson SyndromeMi-Hye Kwon, Chung-Il Joung ··· S222

45. Renal Microaneurysm in a Patient with Systemic Lupus ErythematosusJung Su Eun, Eun Song Lee, Jong Wan Kang, Na Ri Kim,

Sang Jin Lee, Young Mo Kang, Eon Jeong Nam ··· S223

46. A Case of Meningoencephalitis by Cryptococcus Neoformans in a Patient with Systemic Lupus Erythematosus

Do Sik Moon, Hyun-SooK Kim, Yun Sung Kim ··· S224

47. Long-term Outcomes of Autologous Peripheral Blood Stem Cell Transplantation for Refractory Rheumatic Diseases

Seung Lee, Jae-Bum Jun, Chan-Bum Choi, Sang-Cheol Bae ··· S225

48. Tuberculin Skin Test and Interferon Gamma Release Assay (IGRA) for Diagnosing Latent Tuberculosis Infection in Patients with Systemic Lupus Erythematosus

Hyoun-Ah Kim, Hundo Cho, Ye Won Kim, Ju-Yang Jung, Yoo-Jin Um, Jin-Hee Jung, Chang-Hee Suh ··· S226

49. Association of HLA Genes in Systemic Sclerosis with Interstitial Lung DiseaseHyun Mi Kwon, Eun Young Song, Ye Ji Lee, Jin Kyun Park,

Eun Young Lee, Yeong Wook Song, Eun Bong Lee ··· S227

50. Metabolomics for the Diagnosis of Systemic SclerosisKyong-Hee Jung, Sehyun Oh, Won Park, Mie Jin Lim, Seong Ryul Kwon, Sunghyouk Park ··· S228

51. Neutrophil/Lymphocyte Ratio (NLR) were Useful Marker in Prediction of Lung Involvement in Patient with Systemic Sclerosis

Won-Seok Lee, Yun-Jung Choi, Yu-Mi Lee, Wan-Hee Yoo ··· S229

52. Renal Involvement in Patients with Inflammatory Myopathies in KoreaHowook Jeon, Min Seok Choi, Jeniffer Lee, Sung-Hwan Park ··· S230

53. Renal Involvement in Polymyositis: A Case Report Yoon Jeong Oh, Eun Sung Park, Mi Jang, Jeong Hae Kie,

Jason Jungsik Song, YongBeoum Park, Chan Hee Lee, Jin Su Park ··· S231

54. Drug Survival of TNF Alpha Inhibitor in Spondyloarthropathies Using 10 Years of Nationwide Data in Korea: A Population-based Study

Eunyoung Emily Lee, Jeong Seok Lee, Yeong Wook Song, Hee Young Lee, Eun Young Lee ··· S232

55. Lateral Spine BMD Measurement and Trabecular Bone Score Can Represent a Bone Loss in Patients with Advanced Ankylosing Spondylitis

Min Kyung Chung, Jung Hee Koh, Jennifer Lee, Seung-Ki Kwok, Sung-Hwan Park, Ji Hyeon Ju ··· S233

56. Quantitative Assessment of Bone Marrow Fat Using Magnetic Resonance Imaging in Patients with Spondyloarthritis

Bon San Koo, Yoonah Song, Kyung Bin Joo, Seunghun Lee, Tae-Hwan Kim ··· S234

57. Clinical Characteristics of Korean Psoriatic Arthritis Patients: Results from the Nationwide KOBIO Registry

Hyoun-Ah Kim, Seongjun Ha, Seoungjae Choi, Shin-seok Lee, Inkyung Jung, Kichul Shin ··· S235

58. Andersson Lesions of Whole Spine Magnetic Resonance Imaging Compared with Plain Radiography in Ankylosing Spondylitis

Seong-Kyu Kim, Kichul Shin, Yoonah Song, Seunghun Lee, Tae-Hwan Kim ··· S236

59. Estrogen is Associated with Radiographic Progression in Ankylosing SpondylitisHyemin Jeong, Eun Kyoung Bae, Yeong Hee Eun, In Young Kim,

Hyungjin Kim, Joong Kyong Ahn, Jaejoon Lee, Eun-Mi Koh, Hoon-Suk Cha ··· S237

60. Severe Bone Marrow Edema on Sacroiliac Joint MRI Increases the Risk of Low BMD in Patients with Axial Spondyloarthritis

Ha Neul Kim, Joon-Yong Jung, Yeon Sik Hong, Sung-Hwan Park, Kwi Young Kang ··· S238

61. A20 Expression and Bone Remodeling in Ankylosing SpondylitisMin Kyung Lee, Hee Jung Ryu, Mi Ryoung Seo, Hyo Jin Choi, Han Joo Baek ··· S239

62. Phlegmonous Gastritis in Ankylosing SpondylitisBo Young Kim, Shin Ok Jeong, Yoon-Ho Cho, Hyun-sook Kim ··· S240

63. Hypergammaglobulinemia is an Indicator of Extraglandular Manifestations in Patients with Primary Sjogren’s Syndrome

In Je Kim, Roo Min Jun, Jisoo Lee ··· S241

64. Diagnostic Value of Salivary Gland Ultrasonography in Primary Sjögren’s SyndromeJi-Won Kim, Chan Uk Lee, Ji-Na Kim, Jung-Kyu Kim,

Hwajeong Lee, Sung-Hoon Park, Seong-Kyu Kim, Jung-Yoon Choe ··· S242

65. Clinical Characteristics and Treatment outcomes of Patients with Behcet’s Disease with Vascular Involvement

In Young Kim, Yeonghee Eun, Hyemin Jeong, Hyungjin Kim, Jaejoon Lee, Eun-Mi Koh, Duk-kyung Kim, Hoon-Suk Cha ··· S243

66. Sleep Quality and Behcet’s DiseaseJi Min Lee, Hye-Jin Jeong, Chang-Nam Son, Ji-Min Kim, Sang-Hyon Kim ··· S244

67. Potential Laboratory Markers Associated with Disease Activity in Behcet’s DiseaseYunjung Choi, Won seok Lee, Wan-Hee Yoo ··· S245

68. Erosive Arthritis Resembling Osteomyelitis in Behcet’s Disease PatientJae Hyun Jung, Sung Jae Choi, Gwan Gyu Song,

Jong Dae Ji, Young Ho Lee, Jae-Hoon Kim, Young Ho Seo ··· S246

69. Risk Factors for Mortality in ANCA-Associated Vasculitides Gi Bum Bae, Jeong Soo Eun, Na Ri Kim, Eon Jeong Nam, Young Mo Kang ··· S247

70. Clinical Characteristics and Treatment Outcomes of Patients with Large Vessel Vasculitis Including Takayasu Arteritis

In Young Kim, Yeonghee Eun, Hyemin Jeong, Hyungjin Kim, Jaejoon Lee, Eun-Mi Koh, Duk-kyung Kim and Hoon-Suk Cha ··· S248

71. Clinical Characteristics and Treatment Outcomes of Patients with Chronic PeriaortitisIn Young Kim, Yeonghee Eun, Hyemin Jeong, Hyungjin Kim, Jaejoon Lee, Eun-Mi Koh, Duk-kyung Kim and Hoon-Suk Cha ··· S249

72. ANCA is Associated with the Clinical Manifestations of EGPADae-Sik Kim, Jung Yoon Pyo, Se-Jin Byun, Sung Soo Ahn,

Jungsik Song, Yong-Beom Park, Soo-Kon Lee, Sang-Won Lee ··· S250

73. Effect of Teriparatide in Patients with Osteoporosis and Rheumatoid Arthritis Sae Young Lee, Robin Dore, Kenneth Saag, Guillermo Valenzuela,

Kathleen Taylor, Qiu He, Jahangir Alam, Kelly Krohn ··· S251

74. Effect of Urate Lowering Therapy on Renal Disease Progression in Hyperuricemic Patients with Stage 4 Chronic Kidney Disease

Kwanghoon Lee ··· S252

75. The Efficacy and Tolerability of Febuxostat in Hyperuricemic Patients Undergoing DialysisDoo-Ho Lim, Ji Seon Oh, Byeongzu Ghang, Seokchan Hong,

Yong-Gil Kim, Chang-Keun Lee, Seung Won Choi, Bin Yoo ··· S253

76. Identification of Subclinical Tophi in Patients with Gouty Arthritis: A Dual-energy Computed Tomography Study

In Je Kim, Ji Young Hwang, Jisoo Lee ··· S254

77. Clinical Features and Risk Factors of Gout Attacks Following Anti-tuberculous Treatment Sang Wan Chung, Eun Ha Kang, Yun Jong Lee, You Jung Ha ··· S255

78. Increased Carotid Intima-media Thickness was Related with Elevated Serum Homocysteine Level in Patients with Hyperuricemia

Ji Ho Park, Jung-Soo Song, Sang Tae Choi ··· S256

79. Insulin Resistance as an Independent Predictor of Erectile Dysfunction in Patients with GoutJi Hun Kim, Howook Jeon, Seo Hwa Kim, Haneul Kim,

Jihyung Yoo, Min Kyung Chung, Jung Hee Koh, Jennifer Lee, Ji Yeon Lee, Seung-Ki Kwok, Ji Hyeon Ju, Sung-Hwan Park ··· S257

80. MTHFR C677T Polymorphism is Associated with Increase in Homocysteine but not with Uric Acid

Il Woong Sohn, Chan-Bum Choi, Young Seo Kim, Jae-Bum Jun ··· S258

81. Macrophage Migration Inhibitory Factor in GoutHae-Rim Kim, Kyung-Ann Lee, Kyoung-Woon Kim, Bo-Mi Kim, Sang-Heon Lee ··· S259

82. A Case of Cryopyrin Associated Periodic Fever Syndrome (CAPS) with Mutation of NLRP3 as Autoinflammatory Syndrome

Sooyeon Lim, Minji Son, Yumi Seo, Kumi Jeong, Kihwan Kim, Jungwoo Rhim, Seungbeom Han, Jinhan Kang, Myungshin Kim, Daechul Jeong ··· S260

83. Treatment Pattern and Its Cost of Vertebral Fracture among Elderly Patients in KoreaDam Kim, Jeonghoon Ahn, Yoon-Kyoung Sung ··· S261

84. Evaluation of the Inpatient Rheumatology Consultation Service: A Single Tertiary Center Experience

Chan Uk Lee, Sung- Hoon Park, Hwajeong Lee, Ji-Na Kim, Ji-Won Kim, Seong-Kyu Kim, Jung-Yoon Choe ··· S262

85. Utilization Patterns of Medication in Women with Rheumatoid Arthritis of Childbearing Age: Result from KORONA Cohort

Soo-Kyung Cho, Yoon-Kyoung Sung, Dam Kim, Soyoung Won, Hoon-Suk Cha, Jung-Yoon Choe, Chan-Bum Choi, Won Tae Chung,

Seung-Jae Hong, Jae-Bum Jun, Jinseok Kim, Tae-Hwan Kim, Eunmi Koh, Hye-Soon Lee, Jisoo Lee, Shin-Seok Lee, Sung Won Lee, Dae-Hyun Yoo, Sang-Cheol Bae ··· S263

86. The Effect of Rheumatoid Factor on All-cause, Cardiovascular and Cancer-cause Mortality in 296,581 Korean Subjects: A Kangbuk Samsung Health Study

Joong Kyong Ahn, Jiwon Hwnag, Seungho Ryu, Yoosoo Chang ··· S264

87. Prevalence and Incidence of RA and Medical Care Utilization in Elderly Onset RA Patients: An analysis of Korean National Health Insurance Claims Data

Soyoung Won, Soo-Kyoung Cho, Dam Kim, Minkyung Han, Jiyoung Lee, Hyuk Hee Kwon, Eun Jin Jang, Yoon-Kyoung Sung, Sang-Cheol Bae ··· S265

88. Medical Care Utilization among the Korean Patients with Systemic Lupus Erythematosus Seung Lee, Young Bin Joo, So-Yeon Park, Hyuk Hee Kwon,

Hye-soon Lee, Yoon-Kyoung Sung, Sang-Cheol Bae ··· S266

89. A Case of Serotonin Syndrome Following the Administration of Duloxetine in a Fibromyalgia Patient: Case Report and Review of Literature

Joon Sul Choi, Ji Hyun Lee ··· S267

90. Pattern Recognition Receptors in Adult Onset Still’s DiseaseHyoun-Ah Kim, Chang-Hee Suh, Ju-Yang Jung,

Hasan MD Sayeed, Ye Won Kim, Seonghyang Sohn ··· S268

91. TLR4 Endogenous Ligand S100A8/A9 Levels in Adult-onset Still’s Disease and Their Association with Disease Activity and Clinical Manifestations

Hyoun-Ah Kim, Jae Ho Han, Ju-Yang Jung, You-Sun Kim, Chang-Hee Suh ··· S269

92. Cytokine Profiles of Korean Patients with Adult Onset Still’s Disease Treated with Tumor Necrosis Factor Inhibitors

Seung Taek Song, SuMan Kang, Sung Won Lee, Seoung Wan Nam, Dae-Hyun Yoo ··· S270

93. Elevated High Mobility Group B1 Levels in Active Adult-onset Still’s Disease Associated with Systemic Score and Skin Rash

Hyoun-Ah Kim, Ju-Yang Jung, Chang-Hee Suh ··· S271

94. Unbiased Analysis of Fever Curves in Adult Onset of Still’s DiseaseEun Young Ahn, Hyun MI Kwon, Woochang Hwang, Eun Young Lee,

Eun Bong Lee, Yeong Wook Song, Jin Kyun Park ··· S272

95. Serum Uric Acid is Positively Associated with Pulmonary Function in Korean Health Screening Examinees: A Cross-Sectional Study

Jiwon Hwang, Jae-Uk Song, Joong Kyong Ahn ··· S273

96. Clinical Outcomes and Pathological Characteristics of Orbital IgG4-related Disease versus Orbital Inflammatory Pseudotumor

Hong Ki Min, Youn Soo Lee, Suk Woo Yang, Jennifer Lee, Seung-Ki Kwok, Ji Hyeon Ju, Wan-Uk Kim, Sung-Hwan Park ··· S274

97. Are High Levels of Serum B2 Mikroglobuline, Independent Inflammatory Markers from Renal Dysfunction in Geriatric Population?

Suleyman Ozbek, Ertugrul Bayram ··· S275

98. Coexistent Mixed Connective Tissue Disease and Papillary Thyroid Cancer in a Patient with Primary Biliary Cirrhosis: A Case Report

Ji-Heh Park, Seung-Geun Lee, Eun-Kyoung Park ··· S276

(2010. 1. 1∼2010. 12. 31)

The 36th Korean College of Rheumatology Annual Scientific Meeting and the 10th International Symposium

Plenary Session I - International

Free Paper Session

Journal of Rheumatic Diseases Vol. 23, Suppl. 1, May, 2016

S3

Urinary Interleukin-6 as a Predictor of Radiographic Progression in Rheumatoid Arthritis: A 3-year Evaluation

Yune-Jung Park1,2, Seung-Ah Yoo2, Ga-Ram Kim2, Chul-Soo Cho2,3, Wan-Uk Kim2,4

1Department of Internal Medicine, Division of Rheumatology, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon, 2POSTECH-CATHOLIC Biomedical Engineering Institute, The Catholic University of Korea, Seoul, 3Department of Internal Medicine,

Division of Rheumatology, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, 4Department of Internal Medicine, Division of Rheumatology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea

Objectives: Previously, we demonstrated that the urine proteome signature of patients with rheumatoid arthritis (RA)

reflects inflammation-related cellular processes. Here, we measured interleukin (IL)-6, IL-8, and chemokine ligand 2

(CCL2) concentrations in the urine of RA patients and prospectively investigated their role in predicting RA activity and

prognosis.

Methods: One hundred seventy-three RA patients and 62 non-RA controls were consecutively recruited. RA activity

was determined based on assessment of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and 28-joint

disease activity score. Radiographic severity was evaluated using Sharp/van der Heijde score on X-rays of the hands and

feet at 1 and 3 years. Urinary IL-6, CCL2, and IL-8 at presentation were determined by enzyme-linked immunosorbent

assay.

Results: Urinary IL-6, CCL2, and IL-8 levels were elevated in RA patients and correlated well with disease activity.

Urinary IL-6 level at presentation was an independent risk factor of radiographic progression at 1 and 3 years. High uri-

nary IL-6 level increased the risk ratio of radiographic progression by 2.9-fold, which was comparable to high serum CRP.

Moreover, combination of urinary IL-6 and serum CRP measures synergistically increased the predictability of radio-

graphic progression. In a subgroup with normal ESR, patients with the highest tertile of urinary IL-6 were at 6.4-fold

greater risk of radiographic progression.

Conclusions: High urinary IL-6 level at presentation is an independent risk factor for radiographic progression of RA,

reflecting disease activity. Urinary IL-6 in combination with serum CRP may be a useful parameter for estimating RA

prognosis.

O-20-01


S4

Baseline Autoantibodies Preferentially Impact Abatacept Efficacy in Patients with RA Who are Biologic Naïve: 6-Month

Results from a Real-World, International, Prospective Study

Rieke Alten1, Hubert G Nüßlein2, Mauro Galeazzi3, Hanns-Martin Lorenz4, Xavier Mariette5, Alain Cantagrel6, Melanie Chartier7, Guillaume Desachy8, Coralie Poncet9, Christine Rauch10, Manuela Le Bars10

1Schlosspark-Klinik University Medicine, Berlin, 2University of Erlangen, Erlangen, Germany, 3University of Siena, Siena, Italy, 4University Hospital Heidelberg, Heidelberg, Germany, 5Université Paris-Sud, Paris, 6Purpan Hospital, Toulouse, France,

7Chiltern International, Neuilly, 8Excelya, Biostatistician, Paris, 9Docs International, Nanterre, France, 10Bristol-Myers Squibb, Munich, Germany, 11Bristol-Myers Squibb, Rueil-Malmaison, France

Background: In a recent meta-analysis, neither RF nor anti-CCP status were associated with clinical response to an-

ti-TNF treatments. In contrast, anti-CCP positivity may be associated with increased abatacept (ABA) efficacy in prior

bDMARD failure and bDMARD-naïve pts.

Objective: The efficacy of ABA after 6 months' follow-up in bDMARD-naïve pts was compared in RF/anti-CCP positive

vs-negative pts enrolled in the ACTION study.

Methods: ACTION is a 2-year, international, prospective, observational study evaluating retention and effectiveness

of IV ABA in RA pts. Baseline characteristics and clinical outcomes were evaluated at 6 months and compared for

bDMARD naïve anti-CCP/RF-positive and negative pts using analysis of variance on ranks for quantitative variables and

Fisher exact tests for qualitative variables. EULAR response and CDAI was based on DAS28 (ESR or CRP).

Results: In 672 bDMARD-naïve pts, RF was reported in 577 (86%) pts (412 [71%] positive) and anti-CCP in 552

(82%) pts (364 [66%] positive); 308/511 (60%) pts were double positive and 127/511 (25%) pts were double negative.

Clinical outcomes at 6 months were more beneficial in pts who were RF or anti-CCP positive vs negative, including

EULAR good/moderate response vs no response (Figure); mean (95% CI) CDAI (RF: 10.8 [9.8, 11.8] vs 15.3 [13.4,

17.2]; p<0.001; anti-CCP: 10.9 [9.8, 12.0] vs 14.3 [12.4, 16.2]; p=0.002). Similarly, significant differences in clinical out-

comes were observed among pts who were

RF/anti-CCP single or double positive vs dou-

ble negative, respectively, including EULAR

good/ moderate response vs no response

(Figure); mean (95% CI) CDAI (11.1 [10.2,

12.1] and 10.5 [9.3, 11.6] vs 14.5 [12.3, 16.7];

p=0.003 and p=0.001, respectively).

Conclusion: This is the first prospective re-

al-world data showing superior efficacy of ABA

in bDMARD-naïve pts who are RF and/or an-

ti-CCP positive vs negative. The association be-

tween autoantibody status and clinical out-

comes with ABA may be linked to its’

mechanism.

O-20-02


S5

The Effect of Medication on Development of Cardiovascular Disease in Patients with Rheumatoid Arthritis

Soo-Kyung Cho1,2, Dam Kim1,2, Soyoung Won2, Minkyung Han2, Jiyoung Lee2, Eun Jin Jang3, Sang-Cheol Bae1,2, Yoon-Kyoung Sung1,2

1Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, 2Clinical Research Center for Rheumatoid Arthritis (CRCRA), Seoul, 3Department of Information Statistics, Andong National University, Andong, Korea

Objectives: To evaluate the impact of drugs on the development of cardiovascular disease (CVD) in patients with rheu-

matoid arthritis (RA)

Methods: A retrospective cohort of RA patients was established using Korean national healthcare claims database be-

tween Jan 2009 and Dec 2013. There was 6 months disease-free period of CVD to determine the incident cases. After ex-

cluding the patients with CVD history, patients were followed for the development of CVD or the last observational date

(Dec 31, 2013). We performed a nested case-control study of RA patients without previous CVD. Cases who developed

CVD were identified and matched with up to 4 controls without CVD. Controls were matched for age, gender, RA index

date, comorbidities including hypertension, diabetes, hyperlipidemia, chronic kidney disease, and drugs such as anti-

platelet agent, cholesterol lowering agent. Information on drugs exposure: non-steroidal anti-inflammatory drugs

(NSAIDs), disease modifying antirheumatic drugs (DMARDs), biologic DMARDs, corticosteroids, calcium which was

used more than 30 days during 1 year before CVD was collected. Using the multivariate regression model, we evaluate

the impact of drugs on the development of CVD after adjusting various confounding factors.

Results: We identified 7,102 cases and 17,018 controls identified. DMARDs (OR 0.79, 95%CI 0.73-0.85) were pro-

tective effect for CVD. Corticosteroids (OR 1.26, 95%CI 1.19-1.34) and NSAIDs (nonselective NSAIDs: OR 1.32, 95%CI

1.22-1.41, Cox-2 inhibitor: OR 1.31, 95%CI 1.18-1.45) were risk factors for CVD.

Conclusions: DMARDs showed protective effect for CVD, while corticosteroids and NSAIDs were risk factors for

CVD.

O-20-03


S6

Comorbidities of Rheumatoid Arthritis: Results from the 2010-2012 Korean National Health

and Nutrition Examination Survey

Hyemin Jeong1, Sun Young Beak2, Yeong Hee Eun1, In Young Kim1, Hyungjin Kim1, Joong Kyong Ahn3, Jaejoon Lee1, Eun-Mi Koh1, Hoon-Suk Cha1

1Department of Medicine, Samsung Medical Center, 2Biostatic and Clinical Epidemiology Center, Samsung Medical Center, ³Kangbook Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea

Abstract: To evaluate the prevalence of comorbidities in subjects with rheumatoid arthritis (RA) compared with sub-

jects without RA.

Method: The 2010-2012 Korea National Health and Nutrition Examination Survey (KNHANES), which assesses the

general health status of populations in South Korea using interviews and basic health assessment, was analyzed

retrospectively. Weighted prevalence and odds ratio (OR) of comorbidities were analyzed in subjects with RA compared

with subjects without RA.

Results: The overall weighted (n=37,453,158) prevalence of RA was 1.5%. Subjects with RA were older and more fe-

male predominant than subjects without RA. The prevalence of living in urban area, collage graduation, drinking and

smoking was lower in subjects with RA than subjects without RA. Subjects with RA had more comorbidities including

hypertension, dyslipidemia, myocardial infarction (MI) or angina, stoke, osteoarthritis, pulmonary tuberculosis, asthma,

diabetes, depression, thyroid disease and chronic kidney disease. After adjusting socioeconomic and lifestyle character-

istics, RA was associated with increased the prevalence of MI or angina (OR 1.86, 95% CI 1.17 to 2.96, p=0.009), pulmo-

nary tuberculosis (OR 1.95, 95% CI 1.24 to 3.09, p=0.004), asthma (OR 1.97, 95% CI 1.05 to 3.71, p=0.036), depression

(OR 2.38, 95% CI 1.47 to 3.85, p<0.001) and hepatitis B (OR 2.34, 95% CI 1.15 to 4.80, p=0.020). Prevalence of malig-

nancy was not significantly associated with RA.

Conclusions: RA was associated with increased risk of cardiovascular disease, pulmonary tuberculosis, asthma, hep-

atitis B and depression.

O-20-04


S7

Impacts of Disease Activity and Serum Level of Brain-derived Neurotrophic Factor

on Depression in Patients with Rheumatoid Arthritis

Yun-Hong Cheon1, Hyun-Ok Kim1, Young Sun Suh1, Sang-Hyon Kim2, Ji-Min Kim2, Chang-Nam Son2, Seung-Geun Lee3, Eun Kyoung Park3, Sang-Il Lee1

1Department of Rheumatology, Internal Medicine, Gyeongsang National University School of Medicine, Jinju, 2Division of Rheumatology, Department of Internal Medicine, Keimyung University School of Medicine, Daegu,

3Division of Rheumatology, Department of Internal Medicine, Pusan, Korea

Background: Rheumatoid arthritis (RA) and depression is closely associated with each other. The serum level of

brain-derived neurotrophic factor (BDNF) is related with the major depressive disorder (MDD). However, the impacts

of disease activity and BDNF on depression in RA have not well studied.

Objectives: To determine the risk factors for depression and to examine the effect of disease activity and BDNF on de-

pression in patients with RA.

Methods: This cross sectional study was conducted from Jan, 2014 to Jan, 2015 from 3 university hospitals.

Demographic and laboratory data were examined and routine assessment of patient index data 3 (RAPID 3) ques-

tionnaire and 28 joints disease activity score (DAS28-CRP) were assessed for disease activity. Depression was measured

by Korean version of the Beck Depression Inventory second edition (K-BDI II). Serum level of BDNF was assessed by

ELISA.

Results: A total of 507 RA patients were recruited. The prevalence of depression was 46.2% (n=234). RAPID 3 score

showed a significant association with depression in multivariate analysis (OR 1.2, 95% CI 1.1-1.4, P=0.006). The RA pa-

tients with DAS 28-CRP >3.2 (n=135) had more risk for depression than those with DAS 28-CRP<3.2 (n=361) in mul-

tivariate analysis (OR 1.8, 95% CI 1.2-2.8, p=0.006). We re-checked K-BDI II and DAS28-CRP for 29 patients after treat-

ment, and the disease activity and K-BDI II score were improved (ΔDAS28-CRP: -1.73±1.6, and ΔK-BDI II: -7.73±10.8,

P<0.001). In the case of BDNF, there was weakly negative correlation with K-BDI-II score (r=-0.229, P=0.006). The se-

rum level of BDNF was weakly predicted for depression after multiple linear regression analysis with adjustment for co-

variates (β=-0.51, P=0.023).

Conclusion: This study suggests that RAPID 3 score and DAS28-CRP were related with depression. The serum level

of BDNF is negatively related with the severity of depression in patients with RA.

O-20-05

(2010. 1. 1∼2010. 12. 31)


Plenary Session II - International

Free Paper Session


S11

Does Rheumatoid Arthritis Affect Bisphosphonate-related Atypical Femur Fracture?

Jung Hee Koh, Jennifer Lee, Seung-Ki Kwok, Wan-Uk Kim, Sung-Hwan Park, Ji Hyeon Ju

Division of Rheumatology, Department of Internal Medicine, St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Korea

Backgrounds: Patients with rheumatoid arthritis (RA) are diagnosed with osteoporosis earlier than those without, and

are therefore exposed to Bisphosphonates (BP) for longer. However, the increasing use of BPs has raised concerns about

atypical femur fracture (AFF).

Objectives: To determine RA and other clinical factors are associated with an increased risk of BP-related AFF.

Methods: We conducted a retrospective case-control study in patients who have taken BPs for at least 1 year in Seoul

St. Mary’s Hospital, between 2008 and 2015. We identified patients with AFF by reviewing surgical and radiographic

records. Three age- and sex- matched controls without history of AFF were randomly selected to each patient with AFF.

Conditional logistic regression was used to estimate predictors of BP related AFF.

Results: In 35,104 patients who were prescribed BPs for at least a year during 8 year-period, 43 female patients (mean

age, 68.1±7.9 years) suffered AFF (0.12%). The mean length of BPs exposure for them was 7.3±2.7 years. Patients with

AFF had exposed to BPs longer and continued BP treatment without cessation. More patients with AFFs comorbided

with RA than controls did (28% and 7%, respectively, P<0.001). Use of glucocorticoids (GCs) and disease modifying an-

ti-rheumatic drugs (DMARDs) in prior 6 months was more frequently found in patients with AFF. Multivariate logistic

analyses identified prolonged BP exposure (per year, OR, 1.381; 95% CI, 1.168-1.633) without cessation (OR, 5.163;

95% CI, 1.553-17.165), GCs use (OR 13.868, 95% CI, 4.523-42.518), and higher BMI (per kg/m2, OR, 1.456, 95% CI,

1.218-1.743) as being associated with an increased risk of AFF.

Conclusions: Patients receiving long-term BPs without cessation, use of GCs and higher BMI are at higher risk of AFF

than matched control subjects. These patients should be carefully followed up with X-rays or dual energy bone densiom-

etry during BP treatment.

O-20-06


S12

Targeting IL-23 Can Attenuate Progression of Spinal Ankylosis in Ankylosing Spondylitis

Sungsin Jo1*, Bon San Koo2*, Il-Hoon Sung3, Ye-Soo Park4, Tae-Hwan Kim1 1Department of Rheumatology, Hanyang University Hospital for Rheumatic Disease, Seoul, 2Division of Rheumatology, Department of Internal Medicine, Konkuk University College of Medicine, Chungju, 3Department of Orthopaedic Surgery, Hanyang University Hospital for Rheumatic

Disease, Seoul, 4Department of Orthopaedic Surgery, Hanyang University Hospital for Rheumatic Disease, Guri, Korea*These two authors contributed equally.

Background/Objectives: The role of IL- 23 in AS pathogenesis has emerged as a therapeutic target. We investigated en-

doplasmic reticulum (ER) stress and IL-23 cytokine could play a role in human bone derived osteoblast cells and blocking

it leads to regulation of bone-related genes and/or preventing bone ankylosis in AS.

Methods: Primary human osteoblast cells were isolated from diced bones of facet joints which were taken from surgical

operation of 8 AS patients and 8 healthy controls (HC). Osteoblast differentiation- and ER stress-related genes were de-

termined by quantitative RT-PCR, immunoblotting, immunofluorescence, and immunohistochemistry. Osteoblast activ-

ity of all bones-derived osteoblast cells was confirmed by Alkaline Phosphatase activity (ALP) and Alizarin Red (ARS)

staining. The ER stress by BIX, selective BIP inducer X, in the regulation of IL-23 expression and secretion was evaluated.

Results: We found that elevated RUNX2, BIP, and IL-23 protein expressions were observed at osteoblast cells in human

AS compared to HC. In addition, mRNA levels of bone differentiation (ALP, BMP2, COL1A, RUNX2, C/EBPβ, OPG, and

OCN) and ER stress (BIP and CHOP)-related genes were highly expressed in human AS. In particular, IL-23 and RUNX2

expressions were significantly increased in AS. BIX-mediated ER stress stimulated induction of osteoblast activity and

IL-23 secretion via modulating RUNX2 and C/EBPβ genes. Intriguingly, RUNX2 Knockdown by shRNA impeded ER

stress induced effects. Moreover, osteoblast activity and RUNX2 expression in AS were significantly reduced by IL-23

blockers, but not TNFα blockers.

Conclusions: This is the first report to show that osteoblastic activity in AS were increased compared to HC, suggesting

that sustained ER stress induces osteoblast activity and IL-23 expression. Taken together, our results supported that

blocking IL-23 may represent a promising therapeutic target to assist and prevent bony progression in AS.

O-20-07


S13

Impact of Dose Tapering of Tumour Necrosis Factor-blockers on Radiographic Progression in the Ankylosing Spondylitis: A 4-year Prospective Follow Up from Single-centre Cohort

Jun Won Park, MD1, Hyun Mi Kwon, MD1, Jin Kyun Park, MD1, Ja-Young Choi, MD, PhD2, Eun Bong Lee, MD, PhD1, Yeong Wook Song, MD, PhD1, Eun Young Lee, MD, PhD1

1Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, 2Department of Radiology, Seoul National University College of Medicine, Seoul, Korea

Background: Although dose tapering of tumour necrosis factor inhibitor (TNFi) in ankylosing spondylitis (AS) showed

a comparable clinical efficacy in some studies, its impact on radiographic progression remains uncertain.

Objectives: To investigate the impact of dose reduction of TNFi on radiographic progression in the AS over 4 years

Methods: One hundred sixty-five patients treated with etanercept or adalimumab were selected from single-centre,

prospective observational cohort based on the availability of cervical and lumbar radiographs at baseline and after 2-

and/or 4-years of the treatment. Radiographs were assessed by two blinded readers using modified Stokes AS Spinal

Score (mSASSS). Radiographic progression in patients treated with standard-dose TNFi (standard-dose group, n=49)

were compared with patients who tapered the dosage during the treatment (tapering group, n=116) using linear mixed

models.

Results: Baseline characteristics between two groups were comparable except for higher BASDAI (7.1 vs. 6.3,

p=0.003) in the standard-dose group. At 2 years after the treatment, mean dose quotient (SD) of the tapering group was

0.59 (0.17). During the follow up, rate of radiographic progression in overall patients was 0.90 mSASSS unit/year.

Radiographic progression between two treatment strategies was similar after the adjustment for baseline status.

However, in the subgroup of patients with baseline syndesmophyte, it occurred significantly faster in the tapering group

(1.30 vs. 1.82 mSASSS unit/year, p=0.008). It was concordant when radiographic progression was assessed by the num-

ber of newly developed syndesmophyte (0.52/year vs. 0.73/year, p=0.047). Sensitivity analysis after multiple imputation

of missing radiographs also showed similar result.

Conclusion: Dose tapering strategy of TNFi is associated with more rapid radiographic progression in AS patients who

have syndesmophyte at baseline.

O-20-08


S14

Insulin Resistance is Associated with Digital Ulcer in Patients with Systemic Sclerosis

Eun-Kyoung Park, Seung-Geun Lee, Ji-Heh Park

Divsion of Rheumatology, Department of Internal Medicine, Pusan National University School of Medicine, Pusan National University Hospital, Busan, Korea

Background: Growing evidence supports the view that systemic sclerosis (SSc) is a vascular disease mediated by auto-

immunity and evolving into progressive tissue fibrosis. Several vascular biomarkers have been studied, but little is known

about the role of metabolic derangement in vasculopathy in SSc.

Objectives: To investigate the relationship between insulin resistance and digital ulcers (DUs) in patients with SSc.

Methods: Using a cross-sectional design, we recruited 73 consecutive female patients with SSc and 109 sex- and

age-matched healthy controls in South Korea from July 2014 to June 2015. The magnitude of insulin resistance was meas-

ured using the homeostatic model assessment of insulin resistance (HOMA-IR). DUs ever included active and healed

DUs and the extent of skin fibrosis was evaluated using the modified Rodnan skin score (MRSS).

Results: The HOMA-IR in patients with SSc was significantly higher than that in healthy controls (median 1.18 vs.

0.71, p<0.001). In SSc patients, 7 (9.6%) had active DUs and 14 subjects (19.2%) had healed DUs; thus, DUs ever were

observed in 21 cases (28.8%). SSc patients with DUs ever had significantly higher HOMA-IR and MRSS compared with

those without this feature (median, 2.05 vs. 0.99, p=0.001 and 14 vs. 9.5, p=0.011, respectively). After adjustment for

confounding factors using multivariable logistic regression analyses, the HOMA-IR showed a significant positive associa-

tion with the presence of DUs ever in patients with SSc (OR=1.43, 95% CI=1.01-2.05, p=0.048). In addition, higher

MRSS was significantly correlated with DUs ever (OR=1.11, 95% CI=1.02-1.21, p=0.015).

Conclusion: Insulin resistance was independently associated with the presence of DUs in patients with SSc and may

be a potential biomarker for SSc micro-vasculopathy. Moreover, our data also suggest a potential contribution of insulin

resistance to the pathogenesis of DUs.

O-20-09

(2010. 1. 1∼2010. 12. 31)


Invited Lectures I


S17

Treatment of Lupus Nephritis

Bevra H Hahn, MD, UCLA

Professor of Medicine/Rheumatology, UCLA School of Medicine, USA

Bevra H Hahn: Treatment of Lupus Nephritis

S18 Journal of Rheumatic Diseases Vol. 23, Suppl. 1, May, 2016


Journal of Rheumatic Diseases Vol. 23, Suppl. 1, May, 2016 S19


S25

Sequencing Antibody Repertoires to Decipher Pathogenic Mechanisms in Rheumatoid Arthritis

William H. Robinson, MD, PhD

Stanford University School of Medicine, USA

We developed a method that utilizes cell barcodes to enable high-throughput sequencing of the paired heavy-chain and

light-chain immunoglobulin sequences and other co-expressed genes expressed by individual B cells. When applied to

peripheral blood plasmablasts, this approach enables us to generate phylogenetic trees of the acute affinity-matured auto-

antibody response, and thereby pinpoint the antibodies produced in immune responses. We are applying this method to

sequence the antibody repertoire in rheumatoid arthritis (RA). We identified clonal families of B cells that express anti-

bodies specific for citrullinated fibrinogen, citrullinated histones and rheumatoid factor. We characterized the binding

and functional properties of clonal family-derived recombinant antibodies using synovial antigen arrays, macrophage and

neutrophil functional assays, and in mouse models of RA. We identified anti-citrullinated fibrinogen antibodies that du-

al-stimulate macrophage to produce TNF, and anti-citrullinated histone 2B antibodies that form immune complexes that

induce neutrophil netosis. We demonstrate that these antibodies exacerbate the severity of arthritis in mouse models of

RA. Our results are defining novel pathogenic autoantibodies, and elucidating the mechanisms by which they mediate

synovitis and joint tissue destruction, in RA.


S26

Hyperuricemia and Cardiovascular Disease Risk

Hyon Choi, MD, DrPH

Professor of Medicine, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA

Hyperuricemia and gout are strongly associated with cardiovascular (CV)-metabolic-renal comorbidities (e.g., hyper-

tension in 74%, metabolic syndrome in 63%, and obesity in 53% in the US1-4.) and their sequelae (e.g., myocardial in-

farction and premature death5,6). Despite these associations, the causal link between gout (or serum urate) and the risk

of these CV-renal-metabolic outcomes remains unresolved. Recently, with the expansion of genetic discovery through

GWAS, a stronger causal inference became feasible. However, Mendelian randomization studies, which take advantage

of the fact that alleles of an individual’s genotype are assigned randomly at meiosis to eliminate bias by confounding varia-

bles and reverse causation, are particularly relevant in the context of the gout-urate-CVD link as uric acid is associated

with many CV-metabolic risk factor traits. To date, the vast majority of Mendelian Randomization study findings have

been null, suggesting non-causal associations7. In terms of actual randomized controlled trials (RCTs), two RCTs among

adolescents with hyperuricemic prehypertension or stage-1 hypertension found that allopurinol or probenecid lowered

blood pressure with a magnitude of effect similar to the first line oral anti-hypertensive agent,8,9 whereas a similarly de-

signed trial among adults did not find such benefit.10 Importantly, these trials’ participants were not gout patients8-10;

thus, the generalizability of their results remains to be clarified.

Regardless of the question of causality, the high level of major comorbidities and sequelae of gout provide a strong ra-

tionale for serious consideration of these issues in gout care (e.g., choosing appropriate anti-gout therapy) and reducing

the overall disease burden of gout. Observational studies have suggested that allopurinol initiation is associated with a

lower risk of all-cause mortality11,12 and CV events13. A recent study found that the use of colchicine was also associated

with a lower risk of acute coronary syndrome14, unlike the well-established hazardous impacts of NSAIDs and

glucocorticoids.

Taken together, the optimal gout-limiting therapy approaches (pharmacologic, diet, and lifestyle measures) would

adopt a personalized treat-to-target paradigm to reduce both serum urate levels and CV-metabolic-renal complications.

The current low-purine dietary approach to gout offers limited efficacy, palatability, and sustainability, and promotes in-

creased consumption of refined carbohydrates and saturated fat that can actually worsen gout’s CV-metabolic comorbid-

ities by leading to insulin resistance and increased levels of plasma glucose, triglycerides, and LDL-C1,15. In contrast, there

are proven, effective dietary approaches to reduce CV-metabolic conditions (including obesity) that could also lower se-

rum uric acid levels and the risk of gout by lowering adiposity and insulin resistance (which inhibits uric acid excretion).

These existing measures could provide an ideal strategy to reduce both the risk of gout and its associated comorbidities.

For example, the Dietary Approaches To Stop Hypertension (DASH) diet could be investigated for hyperuricemic in-

dividuals with hypertension16, whereas diets against the metabolic syndrome15 could be further examined for obese hy-

peruricemic individuals who require better glycemic control and lipid effects, respectively.

Hyon Choi: Hyperuricemia and Cardiovascular Disease Risk


REFERENCES

1. Fam AG. Gout, diet, and the insulin resistance syndrome. J. Rheumatol. 2002;29(7):1350-1355.2. Choi HK, Mount DB, Reginato AM. Pathogenesis of gout. Ann Intern Med. 2005;143:499-516.3. Choi HK, Ford ES, Li C, Curhan G. Prevalence of the metabolic syndrome in patients with gout: the Third National Health and

Nutrition Examination Survey. Arthritis Rheum. Feb 15 2007;57(1):109-115.4. Zhu Y, Pandya BJ, Choi HK. Comorbidities of Gout and Hyperuricemia in the US General Population - The National Health and

Nutrition Examination Survey 2007-2008. Am. J. Med. In Press.5. Krishnan E, Svendsen K, Neaton JD, Grandits G, Kuller LH. Long-term cardiovascular mortality among middle-aged men with

gout. Arch Intern Med. May 26 2008;168(10):1104-1110.6. Abbott RD, Brand FN, Kannel WB, Castelli WP. Gout and coronary heart disease: the Framingham Study. J. Clin. Epidemiol.

1988;41(3):237-242.7. Merriman TR, Choi HK, Do R, Robinson PC. Mendelian randomization : insights into rheumatological cause-effect relationships.

Nature reviews. Rheumatology. 2016 (in press).8. Feig DI, Soletsky B, Johnson RJ. Effect of allopurinol on blood pressure of adolescents with newly diagnosed essential hypertension:

a randomized trial. Jama. Aug 27 2008;300(8):924-932.9. Soletsky B, Feig DI. Uric acid reduction rectifies prehypertension in obese adolescents. Hypertension. Nov 2012;60(5):1148-1156.

10. McMullan CJ, Borgi L, Curhan GC, Fisher NDL, Forman JP. Effect of Uric Acid Lowering on Ambulatory Blood Pressure: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. J. Am. Soc. Nephrol. 2015(26):43A.

11. Luk AJ, Levin GP, Moore EE, Zhou ZH, Choi HK. Allopurinol and Mortality in Hyperuricemic Patients. Rheumatology (Oxford). 2009;48(7):804-806.

12. Dubreuil M, Zhu Y, Zhang Y, et al. Allopurinol initiation and all-cause mortality in the general population. Ann Rheum Dis. Mar 24 2014.

13. Grimaldi-Bensouda L, Alperovitch A, Aubrun E, et al. Impact of allopurinol on risk of myocardial infarction. Ann Rheum Dis. Jan 6 2014.

14. Solomon DH, Liu CC, Kuo IH, Zak A, Kim SC. Effects of colchicine on risk of cardiovascular events and mortality among patients with gout: a cohort study using electronic medical records linked with Medicare claims. Ann Rheum Dis. Nov 18 2015.

15. Dessein PH, Shipton EA, Stanwix AE, Joffe BI, Ramokgadi J. Beneficial effects of weight loss associated with moderate calo-rie/carbohydrate restriction, and increased proportional intake of protein and unsaturated fat on serum urate and lipoprotein levels in gout: a pilot study. Ann Rheum Dis. 2000;59(7):539-543.

16. Juraschek SP, Gelber AC, Choi HK, Appel LJ, Miller ER, 3rd. Effects of the Dietary Approaches To Stop Hypertension (DASH) Diet and Sodium Intake on Serum Uric Acid. Arthritis and Rheumatism (in press). 2016.

(2010. 1. 1∼2010. 12. 31)


Luncheon Symposium and Lunch Break


S31

Tofacitinib, an Oral Janus Kinase Inhibitor, as Monotherapy or with Background Methotrexate,

in Japanese Patients with Rheumatoid Arthritis: An Open-label, Long-term Extension Study

Hisashi Yamanaka1*, Yoshiya Tanaka2, Tsutomu Takeuchi3, Naonobu Sugiyama4*, Hirotoshi Yuasa4, Shigeyuki Toyoizumi4, Yosuke Morishima4, Tomohiro Hirose4, Samuel Zwillich5

1Institute of Rheumatology, Tokyo Women’s Medical University, Tokyo, 2The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, 3Department of Internal Medicine, Keio University, Tokyo,

4RA & Inflammation Medical Affairs, Pfizer Japan Inc, Tokyo, Japan, 5Pfizer Inc, Groton, Connecticut, USA

Background: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. Here, tofacitinib

safety and efficacy data from a long-term extension study in Japanese patients are presented.

Methods: Study A3921041 was a multi-centre, open-label, long-term extension study that included Japanese patients

who had participated in a prior Phase 2 or Phase 3 study of tofacitinib as monotherapy or with background methotrexate.

Patients received tofacitinib 5 mg twice daily (BID) or tofacitinib 10 mg BID. Dose adjustment of tofacitinib during treat-

ment period, and concomitant usage of disease-modifying antirheumatic drugs including methotrexate after week 12

were permitted. Primary endpoints were adverse events, laboratory parameters and vital signs. Secondary efficacy end-

points included American College of Rheumatology (ACR)20/50/70 response rates, Disease Activity Score (DAS)

28-4(erythrocyte sedimentation rate (ESR))<2.6 response rate (DAS-defined remission) and Health Assessment

Questionnaire-Disability Index (HAQ-DI) score. Safety and efficacy data were assessed throughout the study.

Results: A total of 486 patients were recruited and treated (1439.9 patient-years of exposure). 308 patients completed

the study. Median (range) duration of treatment in this extension study was 1185 (5-2016) days. 476 patients (97.9%)

experienced adverse events; the majority of which (97.8%) were of mild or moderate severity. The two most common

treatment-emergent adverse events were nasopharyngitis (n=293, 60.3%) and herpes zoster (n=94, 19.3%). For all tofa-

citinib-treated patients, the incidence rate (patients with events per 100 patient-years) was 10.7 for serious adverse

events, 3.3 for serious infections, 7.4 for herpes zoster (serious and non-serious) and 1.2 for malignancies (excluding

non-melanoma skin cancer). Mean changes from baseline(start of the index study) in laboratory parameters were con-

sistent with those seen in previously reported studies of tofacitinib. ACR20/50/70 response rates, DAS-defined re-

mission rates and HAQ-DI scores were sustained through to study completion.

Conclusions: Tofacitinib (with or without background methotrexate) demonstrated a stable safety profile and sus-

tained efficacy in Japanese patients with active rheumatoid arthritis. The risk of herpes zoster appears to be higher in

Japanese patients treated with tofacitinib than in the global population.

(2010. 1. 1∼2010. 12. 31)


Issues in Clinic Session


S35

BP & HCQ Uses in Rheumatic Diseases

이창근

울산대학교 의과대학 서울아산병원

이창근: BP & HCQ Uses in Rheumatic Diseases



S42

Rhuematism as a co-morbidity of Medication Related Osteonecrosis of the Jaws (MRONJ)

Yong-Dae Kwon, DMD, MSD, PhD

Department of Oral & Maxillofacial Surgery, Center for Refractory Jawbone Diseases, Kyung Hee University Dental Hospital

Bisphosphonate has been regarded as one of the major risk factors of MRONJ and other medications like Denosumab

may be also a risk factor of ONJs. Although the incidence of MRONJ is still ambiguous, the incidence from oral bi-

sphosphonate is believed less than 0.01%.

MRONJ has really multifactorial etiology and is a consequence of local and systemic triggers. There are many etiologic

factors besides bisphosphonate. Many elderly ladies are suffering from rheumatism and osteoporosis. DMRADs are com-

prised of steroid, cytotoxic drugs and immunosuppressive agents. Long-term antirheumatic therapy may impair bony

healing. It is well known that long-term steroid can induce osteoporosis and this may lead to higher chance of bi-

sphosphonate therapy.

Oral cavity is basically contaminated area with various oral microbes and the mucosal barrier is quite thinner than that

of ordinary skin. Surgical procedures involving bone is commonly carried out in the alveolar bone. Long-term DMRADs

may hinder healing process when dental surgeries involving alveolar bone were performed.

Actually, there is a lack of evidence showing the direct relationship between MRONJ and RA but there are several possi-

ble hypotheses linking long-term DMRADs and ONJs. It is well-known that GDTC may play a role in an anti-

body-dependent cell-mediated cytotoxic reaction toward the epithelium of the oral mucosa, which may be a reason de-

layed soft tissue healing in MRONJ patients. In RA patients, pro-inflammatory cytokines are elevated and may reach jaw-

bone as well. The relationship between RA and periodontal disease (PD) has been widely investigated and it might be

postulated that ONJs may have a link to RA. PD can be one of the risk factors of ONJs but the microbiologic implication

of specific pathogens has not been confirmed.

It may be reasonable to expect an increased tendency in the number of MRONJ lesions in RA patients considering that

rheumatologists in many countries may be less familiar to this disease than bone specialists are and that BPs are the most

frequent prescribed drugs in rheumatologic practice. This is due to the high efficiency of BPs in the prevention and treat-

ment of osteoporosis, which is a common feature in RA.

Many dentists are aware of MRONJ and long-term bisphosphonate can be a risk of ONJs. However, many of them are

not aware that long-term antirheumatic therapy may also contribute to impaired bony healing after invasive dental sur-

gery such as dental implant placement and they often fails to deliver the informed consent that rheumatism and its treat-

ment may affect the outcome of a dental surgery involving alveolar bone.

In this presentation, rheumatism as one of risk of MRONJ will be discussed.


S43

Screening for Hydroxychloroquine Retinopathy: Why and How?

김상진

성균관대학교 의과대학 삼성서울병원 안과

김상진: Screening for Hydroxychloroquine Retinopathy: Why and How?


(2010. 1. 1∼2010. 12. 31)


Healthcare Policy Symposium


S49

2016년 의료질 평가

정통령

보건복지부 보험급여과

정통령: 2016년 의료질 평가



S56

류마티스 및 근골격계 질환의 질병 부담 및 질관리 현황

이은봉

서울대학교 의과대학 내과학교실

류마티스 및 근골격계 질환은, 인체에서 가장 큰 기관을 침범하는 질환들로서, 다양한 질환을 포함한다. 세계보건기구 주관으로 진행

된, 대표적 질환에 대한 질병 부담 연구에 따르면, 근골격계 질환의 대표 질환인 요통은 장애로 인한 손실 년수 측면에서 전세계적으로

가장 질병 부담이 큰 질환이며, 국내에서도 요통의 생애 유병률은 50%를 상회한다. 퇴행성 관절염도, 노인인구에서 발생하는 흔한 질환

으로서 장애로 인한 손실 년수로 비교했을 때, 전세계적으로 11번째로 질병부담이 큰 질환이며, 국내에서의 유병률은 10% 이상에 달한

다. 이외에도 류마티스 관절염, 통풍 관절염, 견통 등 다양한 근골격계 질환들은 비교적 흔하게 발생하는 질환들로서, 이환된 환자에게

장기적인 장애를 유발해서, 질병부담을 가중시킨다. 특히 근골격계 질환의 대부분이, 완치가 불가한 질환들이어서, 인구고령화에 따라

근골격계 질환에 따른 질병부담은 점차 늘어날 것으로 예상된다. 류마티스 및 근골격계 질환이 적절하게 치료되고 있는지를 평가하기

위해서 객관화된 질 지표를 이용한 질 평가가 다양하게 시도되고 있다. 질 평가는 아직까지는 주로, 치료과정에 대한 평가를 중심으로

이루어지고 있으며, 류마티스 관절염의 경우 전체적으로 60% 내외, 퇴행성 관절염의 경우 40% 내외의 지표 달성률을 보인다. 따라서

근골격계 질환의 치료의 질은 아직도 개선할 여지가 많은 것으로 간주되고 있으며, 현재 치료의 질을 객관적으로 평가할 수 있는 도구의

개발과 현재 상황에 대한 객관적인 평가가 필요할 것으로 보인다.


S57

류마티스관절염 질지표 개발과 적용

백한주

가천대학교 의과대학

최근 국내외적으로 의료의 각 분야에서 진료의 질에 대한 문제제기 및 질 향상을 위한 논의가 이루어졌다. 류마티스 내과 전문의는

근골격계 환자에게 양질의 진료를 제공할 의무가 있다. 이를 위해서는 질 측정 및 평가, 질 향상을 위한 활동에 참여해야 한다.

류마티스관절염은 조기 진단과 적절한 치료로 질병의 비가역적 결과와 합병증을 막을 수 있을 가능성이 높은 질환이지만 외국의 여려

연구들에서 진단과 치료가 적절히 이루어지지 않는다는 점을 보여 주었다. 그래서 현재 외국에서는 다양한 류마티스관절염 질 지표가

각 국가의 의료체계 내에서 류마티스관절염의 질 측정에 적용하기 위해 새로이 개발되고 있다. 우리는 한국의 류마티스 관절염 진료의

질을 측정하기 위한 질 지표를 개발하고자 했다.

질 지표 개발은 RAND/University of California at Los Angeles appropriateness Method를 우리 실정에 맞게 수정하여 이용하

였다. 문헌 고찰을 통해 후보 질 지표를 선정하고 전문가 패널 토의를 통해 질 지표를 선정하였다. 후보 질 지표 선정에는 외국의 기존

질 지표 및 진료 지침, 한국의 류마티스관절염 진료 지침, 결핵 진료 지침 등을 참고하였다. 전문가 패널 토의는 두 차례에 걸쳐서 이루어

졌고 첫 번째 토의에서는 의학적 적절성에 대한 평가가 있었고 두 번째 토의에서는 질 지표의 적용성에 대한 평가가 있었다.

후보 질 지표는 70개가 선정되었고 첫 번째 전문가 패널 토의에서 56개의 후보 질 지표가 적절한 것으로 평가되었다. 두 번째 전문가

패널 토의에서는 첫 번째 토의에서 적절한 것으로 평가된 56개의 질 지표 후보와 그 측정을 적용성에 대해 평가하였고 15개의 질 지표

후보가 최종적으로 적합한 것으로 선정되었다. 향후 이 지표의 정확성과 재현성, 현장에서의 임상적 유용성에 대한 검증 및 확인이 필요

할 것이다.

(2010. 1. 1∼2010. 12. 31)


REOPHARD Session


S61

REOPHARD: History of the Registry and Analysis of Baseline Data

전찬홍

순천향대학교 의과대학

Objectives: Registry of Pulmonary Arterial Hypertension associated with Rheumatic Disease (REOPHARD) was ini-

tiated to observe the characteristics of connective tissue disease (CTD) associated pulmonary arterial hypertension

(PAH) in Korean patients. The baseline data from the second year of the registry’s operation were described.

Methods: Patients with CTD who met the modified definition of the WHO group I PAH were enrolled. Hemodynamic

parameters and clinical data such as demographics, functional class, underlying disease, organ involvement, laboratory

tests and treatments were recorded. Baseline data collected from April 2008 to March 2010 were investigated.

Results: A total of 321 patients were enrolled. The mean age of the patients at registration was 51.9 years and 87.5%

were female. Most patients were diagnosed by echocardiography and only 24 patients (7.5%) underwent cardiac

catheterization. Exertional dyspnea was present in 63.6% of patients and 31.8% were New York Heart Association class

III or IV. Among the patients, systemic lupus erythematosus accounted for 35.3%, systemic sclerosis 28.3%, rheumatoid

arthritis 7.8%, overlap syndrome 9.0%, and mixed connective tissue disease 5.9%. There were no significant differences

in hemodynamics, functional class, diffusing capacity and N-terminal pro-brain natriuretic peptide levels between the

disease subgroups. Treatments consisted of calcium antagonists (57.0%), endothelin antagonists (32.7%), prostanoids

(27.1%), phosphodiesterase-5 inhibitors (14.3%) and combinations (37.4%).

Conclusions: REOPHARD was the first nation-wide survey of Korean patients with CTD-PAH. Compared with pre-

vious studies, the results showed some differences: underlying diseases, functional status and treatments.


S62

Survival and Prognostic Factors in Patients with Connective Tissue Disease-associated Pulmonary Hypertension by

Echocardiography: Results from a Korean Nationwide Registry

Kwi Young Kang1, Chan Hong Jeon2, Sung Jae Choi3, Bo Young Yoon4, Chan-Bum Choi5, Chang Hoon Lee6, Chang-Hee Suh7, Choong Won Lee8, Chul Soo Cho9, Eon Jeong Nam10, Eun-Mi Koh11, Ho-Youn Kim9, Hyo Jin Choi12, Hyoun-Ah Kim7, Jae-Bum Jun5, Jaejoon Lee11, Jinseok Kim13, Jong Dae Ji3,

Jun Ki Min9, Ki Jo Kim9, Kichul Shin14, Min Wook So15, Seong Ryul Kwon16, Seong-Kyu Kim17, Seong-Su Nah18, Seung-Ki Kwok9, Soo-Kon Lee19, Sung Won Lee20, Sung-Hwan Park9, Won Park16,

Yong-Beom Park19, Young Ho Lee3, Shin-Seok Lee21*, Dae Hyun Yoo5*1Department of Internal Medicine, Incheon Saint Mary’s Hospital, Catholic University of Korea, Incheon, 2Department of Internal Medicine,

Hospital Bucheon, Soonchunhyang University, Bucheon, 3Division of Rheumatology, Department of Internal Medicine, College of Medicine, Korea University, Seoul, 4Departments of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang,

5Department of Internal Medicine, College of Medicine, Hanyang University, 6Departments of Internal Medicine, Wonkwang University College of Medicine, Iksan, 7Department of Rheumatology, Ajou University School of Medicine, Suwon, 8Department of Internal Medicine,

Wallace Memorial Baptist Hospital, Busan, 9Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, 10Department of Internal Medicine, Kyungpook National University School of Medicine, 11Department of Internal Medicine, Sungkyunkwan University, 12Division of Rheumatology, Department of Internal Medicine, Gachon University Gil Medical Center,

Incheon, 13Departments of Internal Medicine, Jeju National University School of Medicine, Jeju, 14Department of Internal Medicine, Seoul National University, Borame Hospital, 15Department of Internal Medicine, Asan Medical Center, University of Ulsan college of Medicine, Seoul,

16Departments of Internal Medicine, Inha University College of Medicine, Incheon, 17Department of Internal Medicine, Catholic University of Daegu, 18Department of Internal Medicine, Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan,

19Department of Internal Medicine, Yonsei University College of Medicine, Seoul, 20Department of Internal Medicine, College of Medicine, Dong-A University, Pusan, 21Department of Rheumatology, Chonnam National University Medical School, Kwangju, Korea

Objectives: Pulmonary arterial hypertension (PAH) is a major cause of mortality in connective tissue disease (CTD).

The survival rates and mortality-predictive factors of a nationwide registry of Korean patients with CTD-PH measured

by echocardiography were determined.

Methods: Patients with CTD-PH were enrolled between April 2008 and December 2012. Hemodynamic parameters

and clinical data (WHO-functional class [FC], organ involvement, laboratory tests, and treatment agents) were recorded.

Survival rates were calculated by using the Kaplan-Meier method. Mortality-associated factors were examined by Cox

proportional hazards regression analysis.

Results: In total, 174 incident PH cases (61 with SLE, 50 with systemic sclerosis, 10 with mixed CTD, 22 with RA, and

31 with other CTDs) were diagnosed by Doppler echocardiography. Of these, 25 (14%) died during the 3.8±2.7 year fol-

low-up period after PH diagnosis. The 1 and 3 year survival rates were 90.7% and 87.3%, respectively. Compared to the

other CTD- PH s, RA- PH had the lowest survival rates (56% 3 year survival; p=0.022). Multiple regression analysis re-

vealed that low DLCO, pleural effusion, and diabetes mellitus were poor prognostic factors (p=0.008, 0.04, and 0.009,

respectively). Anti-UI-RNP antibody positivity was protective (p=0.022). In patients with WHO-FC III/IV, patients who

received vasodilators had lower mortality than those who did not (p=0.038).

Conclusions: In Korean patients with CTD- PH, the 3 year survival rate was 87%. Low DLCO, pleural effusion, and dia-

betes mellitus were independent poor prognostic factors. Anti-UI-RNP antibody was protective. Prompt PAH-specific

vasodilator therapy may improve the survival of patients with severe CTD- PH.


S63

KORPAH Registry 데이터의 분석

최성재

고려대학교 의과대학

KORPAH REGISTRY

이 연구의 목적은 한국 폐동맥 고혈압 환자의 유병률, 증상, 성별, 나이, 병인과 치료 등을 알아보는 것으로 2008년부터 2011년까지

환자를 등록해 연구를 진행하였다.

심장내과, 류마티스내과, 호흡기내과, 소아청소년과 4분과의 625명 환자로 연구를 시작했다. 가장 많은 병인은 결합조직 질환으로

전체의 49.8%이고, 선천성 심장 질환은 25.4%, 특발성이거나 가족력에 의한 경우는 23.2%였다. 피험자의 평균나이는 47.6세, 성별

은 여자:남자 비율이 4:1 정도로 여자가 많았으며, 피험자의 특성이 세계 여러 나라의 registry의 피험자 특성과 비슷했다. 피험자의 분

류는 WHO-NYHA Class가 III와 IV 단계인 중증의 환자가 43.3%였다. 특발성 환자(IPAH)와 다른 질환과 관련된 환자(APAH)간

에 Class, 성비, 6MWD에서 차이가 없었지만, DLCO (폐확산능)이 낮은 폐 질환이 있는 환자는 APAH 환자 중 결합조직 질환과 관련

된 환자에게서 많았다. 표적 요법은 47% 환자가 받고 있었고 이 환자들이 주로 쓰는 약제는 bosentan으로 47%였다. WHO Class

III 혹은 IV인 환자 중 표적 요법으로 치료받은 환자는 62.8%이고 이 중 가장 많이 사용되는 약은 bosentan으로 35.7%였다. 진단 도구

는 심초음파가 60%, 우심도자술이 40%였다.

새로 발병한 환자들에 대한 특성

새로 발병한 환자 297명을 따로 비교했을 때, 한국의 유병률은 매년 백만명당 1.9명이 발병했고, 다른 나라 연구에서도 인구 백만명

당 2.0명이 발생하므로 우리나라 유병률과 비슷하다. 새로 발생한 환자들의 평균 나이(50세)와 성별(여성, 78.5%)도 전체 피험자와

거의 비슷했다. 이들의 병인은 결합조직 질환이 57.6%로 가장 많았고 Class도 II와 III가 전체의 74%를 차지했다. IPAH와 APAH를

비교했을 때, 결합조직 질환과 관련된 환자가 가장 많았고, 성별, 나이, Class나 수축기 혈압에서 두 군 간에 특별한 차이는 없었다. 단일

표적 치료는 52%, 병용 요법은 9%였으며, 가장 많이 투여한 제제는 bosentan이었고 병용요법에 가장 많이 쓰인 제제는 bosentan과

sildenafil이었다. 이 환자들의 진단 도구는 심초음파가 64.3%로 가장 많았고, 새로 발병한 환자 297명 중 우심도자술을 시행한 환자는

106명이었고 우심도자술을 시행한 환자 중 IPAH와 APAH 간에 큰 차이는 없었다.

생존율에 영향을 미치는 요인

297명 환자 중 1.7년 간 35명의 사망이 있어서 매년 100명 중 7명의 사망을 보였다. 결합조직 질환과 관련된 환자들이 가장 높은

사망률을 보였다. 생존율은 12개월에 90.8%, 24개월 87.8%를 보였다. 2010년의 REVEAL 연구의 12개월 생존율 90%와 비슷했고

이 연구에서도 IPAH 환자보다 APAH 환자들의 생존율이 더 낮았고 다른 나라 연구들도 이와 유사했다. 결합조직 질환과 관련된 환자와

WHO-NYHA Class III, IV 환자들의 누적 생존율이 가장 낮았다. 6분 보행검사 시 380 m 이하로 달린 환자와 NT-ProBNP가 797

ng/ml 이하인 환자의 생존율이 낮았다. 또한, 표적 치료를 받은 환자가 통상적 치료를 받은 환자보다 생존율이 높았다. Class 분류와

치료요법, NT Pro-BNP가 의미 있는 인자였으나 BNP나 pericardial effusion은 통계적으로 의미를 보이지 않았다. 생존율에 가장

영향을 미치는 인자는 Class 분류와 표적치료 여부였다.

최성재: KORPAH Registry 데이터의 분석


결 론

가장 첫 번째로 이뤄진 전국적인 registry였고, 그 당시 임상 치료를 잘 반영했으며 다른 외국 연구 결과와 유사했다. 사망률은 매년

100명당 7명이었으며, 1년 생존율은 90.8%, 2년 생존율은 87.8%였으며, 생존율에 관련된 인자는 Class와 표적 치료 여부였다. 앞으

로 이 연구 결과를 기반으로 더욱 심층적인 국내 환자에 대한 연구 결과를 얻을 수 있겠다.


S65

Progression and Outcomes in Patients with Pulmonary Artery Hypertension Associated with Systemic Rheumatic Diseases:

Results from a Korean Nationwide Registry

MR Seo, HJ Ryu, HJ Choi, HJ Baek

Department of Internal Medicine, Division of Rheumatology, Gachon University Gil Medical Center, Incheon, Korea

Background: Pulmonary artery hypertension (PAH) is associated with mortality and morbidity in patients with rheu-

matic diseases.

Objectives: To investigate the progression and outcomes in patients with PAH associated with systemic rheumatic

diseases.

Methods: We used the data from the REgistry of Pulmonary Hypertension Associated with Rheumatic Disease

(REOPARD). The patients who had the results of systolic pulmonary artery pressure (sPAP) by echocardiography at the

time of diagnosis of PAH and at least one year later were enrolled.

Results: A total of 198 patients were included and female to male was 8:1. Age at the diagnosis of PAH was 46.9±14.8

years. The associated systemic rheumatic diseases were systemic sclerosis (32.8%), systemic lupus erythematosus

(32.8%) and others (34.3%). The sPAP at the time of diagnosis was 57.2±18.8 mmHg. Patients were classified into three

groups. The improvement group who sPAP was improved more than 30% were 57 patients (28.8%). The aggravating

group who sPAP was aggravated more than 30% were 40 patients (20.2%). The stationary group who were not both of

them were 101 patients (51.0%). The time intervals of echocardiography were 50.9±29.5 months in the improvement

group, 47.7±26.3 months in the stationary group, and 63.3±40.2 months in the aggravating group (p=0.02). The pa-

tients who died by any causes were 5.4% in the improvement group, 19.0% in the stationary group, and 43.2% in the ag-

gravating group (p<0.01). The patients with WHO-functional class III/IV were 22.2% in the improvement group, 47.4%

in the stationary group, and 81.1% in the aggravating group (p<0.01). The patients with home oxygen therapy were 1.8%

in the improvement group, 10.9% in the stationary group, and 22.5% in the aggravating group (p<0.01). The factors as-

sociated with deterioration of sPAP were systemic sclerosis, history of ischemic ulcers, and arrhythmia. The factors asso-

ciated with favorable outcomes of sPAP was history of pleural effusion (p<0.05).

Conclusion: The deterioration of sPAP was associated with worse outcomes in systemic rheumatic diseases patients

with PAH and it was associated with systemic sclerosis, history of ischemic ulcers, and arrhythmia.

(2010. 1. 1∼2010. 12. 31)


Free Paper Session: Rheumatoid Arthritis

Clinical Aspects I


S69

Baseline Profiles in Korean Patients with Rheumatoid Arthritis when Initiating or Switching Biologic Agents:

Results from the KOBIO Registry

Dong-Jin Park, Ji-Hyoun Kang, Yi-Rang Yim, Ji-Eun Kim, Jeong-Won Lee, Kyung-Eun Lee, Lihui Wen, Tae-Jong Kim, Yong-Wook Park, Shin-Seok Lee

The Division of Rheumatology, The Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea

Objective: Despite improved clinical outcomes for the majority of rheumatoid arthritis (RA) patients, RA patients fre-

quently experience treatment failure with one biologic agent, due to either inefficacy or adverse events, and switch to

another. This study investigated the pattern of biologic treatment and the reasons for switching biologics in Korean pa-

tients with RA

Methods: Patients with RA who had been started on a biologic agent or had switched to another biologic agent were

identified from the prospective observational Korean nationwide Biologics (KOBIO) registry. The KOBIO registry en-

rolled 1184 patients with RA at the time of initiation or switching of biologic agents. Patients were categorized according

to the chronological order of the introduction of biologic agents, and the reasons for switching of biologics were also

evaluated.

Result: Of the 1184 patients with RA, 801 patients started with their first biologic agent, 228 patients were first time

switchers, and 89 patients were second time or more switchers. Second or more switchers had lower rheumatoid factor

(RF) and anti-CCP positivity and higher disease activity scores (i.e., DAS28, SDAI, and CDAI score) at the time of enroll-

ment than the other groups. In these patients, tocilizumab was the most commonly prescribed biologic agent, followed

by adalimumab, and etanercept. The most common reason for switching biologics was inefficacy (76.2%), followed by

adverse events (14.5%), which included infusion reaction (6.2%), infection (2.5%), and skin eruption (1.8%).

Conclusion: In this registry, we found different baseline profiles based on the chronological order of biologic agents.

O-20-10


S70

Drug Survival of Biologic Agents in Rheumatoid Arthritis Using 10 Years of Nationwide Data in Korea:

A Population-based Study

Jeong Seok Lee1, Jun Won Park1, Eunyoung Emily Lee1, Yeong Wook Song1, Hee Young Lee2, Eun Young Lee1*1Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Seoul,

2Center for Preventive Medicine and Public Health, Seoul National University Bundang Hospital, Seongnam, Korea

Background: Since 2004, Korean national health insurance began to cover the cost of biologic agents in rheumatoid ar-

thritis (RA) patients experiencing treatment failure by conventional disease modifying antirheumatic agents. However,

real-world issues such as selecting or switching among biologic agents in clinical practice became more complicated as

types of the agents increased.

Objectives: To evaluate 1) first choice among biologic agents, 2) drug retention rate and duration of each biologic agent

in RA.

Methods: We used retrospective cohort data from the National Health Insurance Service in Korea, which consisted of

more than one million subjects representing whole Korean population followed from 2004 to 2013. All RA patients with

any experience of biologic agents were checked. We also compared with the independent cohort of biologic agent users

in Seoul national university hospital.

Results: One hudred and seventy three patients were found to experience any of TNFa inhibitors. Etanercept was the

most frequent choice as first TNFa inhibitor (43.4%). Among TNFa inhibitors, retention rates of etanercept at month 12

and 24 were significantly higher than adalimumab and infliximab (Fig. 1A-B). Mean duration of retention was almost

twice longer in etanercept than others (Fig. 1C-D).

Conclusions: This research can be a pilot study before analyzing nationwide population cohort encompassing whole

population of Korea. Conclusively, etanercept has been prescribed longer in general and the rate of retention till 2 years

was also better than adalimumab and infliximab for 10 years after national insurance coverage.

O-20-11


S71

Efficacy and Safety of Add-on Treatment of Tacrolimus versus Leflunomide in Rheumatoid Arthritis

Patients with Inadequate Response to Methotrexate

Kichul Shin1, Han Joo Baek2, Young Mo Kang3, Hoon-Suk Cha4, Seong Wook Kang5, Sung-Hwan Park6, Jae Bum Jun7, Yun Jong Lee8, Yeong Wook Song9,10

1Division of Rheumatology, SMG-SNU Boramae Medical Center, Seoul, 2Division of Rheumatology, Department of Internal Medicine, Gachon University Gil Hospital, Incheon, 3Division of Rheumatology, Department of Internal Medicine, Kyungpook National University

Hospital, Daegu, 4Division of Rheumatology, Department of Internal Medicine, Sungkyunkwan University, Samsung Medical Center, Seoul, 5Division of Rheumatology, Department of Internal Medicine, Chungnam National University Hospital, Daejeon, 6Division of Rheumatology, Department of Internal Medicine, Catholic University of Korea, Seoul St Mary’s Hospital, Seoul, 7Division of Rheumatology, Department of

Internal Medicine, Hanyang University, Hospital for Rheumatic Disease, Seoul, 8Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, 9Division of Rheumatology, Department of Internal Medicine, Seoul National University

Hospital, Seoul, 10Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine, Medical Research Institute, Seoul National University, Seoul, Korea

Background: Tacrolimus (TAC) is a disease modifying antirheumatic drug (DMARD) used for rheumatoid arthritis

(RA) treatment. Combination of TAC with methotrexate (MTX) was shown to be effective and safe in RA, yet com-

parative clinical studies are insufficient to date.

Objective: To investigate the efficacy and safety of TAC versus leflunomide (LEF) when combined with MTX in RA

patients.

Method: The PLATINUM-X study is a 24-week multi-center, double-blinded randomized non-inferiority (phase 4)

study targeting RA patients with moderate to active disease activity (DAS28(ESR)>3.2) who previously had an in-

adequate clinical response to MTX. Patients were randomized into the TAC or LEF (add-on to MTX) group. The initial

daily dose of TAC and LEF were 1.5 mg and 10 mg, respectively, for 4 weeks then increased to 3 mg, 20 mg per day until

the end of the study. Clinical and laboratory data were obtained at 4, 8, 16, and 24 weeks. The primary endpoint was to

compare DAS28 at 24 weeks. The per protocol set was used for statistical analysis.

Result: Eighty seven patients were screened in 9 centers, and 75 patents were randomized into 2 groups. Baseline dem-

ographics of patients were comparable with baseline DAS28 being 4.54±0.61 and 4.91±1.01 in the TAC and LEF group,

respectively. TAC was non-inferior to LEF in terms of reduction of DAS28 at 24 weeks (mean difference -0.0565, CI

-0.6513, 0.5384). Improvement of DAS28, K-HAQ throughout each visit was not statistically different between the 2

groups. Yet, reduction in tender joint count was significant in the TAC group compared with LEF (-5.97±4.89 versus

-3.08±5.55 at 24 weeks, p=0.0145). Six patients presented transaminitis in the LEF group compared with 2 in the TAC

group.

Conclusion: The efficacy of TAC plus MTX was non-inferior to LEF combined the MTX, with a reasonable safety profile

in RA patients with moderate to active disease activity.

O-20-12


S72

The Impact of Korean Red Ginseng on Disease Activity and Improvement of Fatigue in Patients with Rheumatoid Arthritis:

A Randomized, Double-blind, Crossover Study

Soo-Kyung Cho, DasomiYoo, Dam Kim, Yoon-Kyoung Sung

Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea

Background and Objective: Patients with rheumatoid arthritis (RA) suffer from fatigue, apart from pain and disability.

In this randomized, crossover clinical trial, we aimed to evaluate the impact of Korean Red Ginseng (KRG) on disease ac-

tivity and improvement of fatigue in RA patients.

Methods: Eighty of RA patients were randomly allocated to KRG (2 g/day, n=40) or placebo (n=40) groups for the

first 8 weeks, followed by crossover to the other arm for the final 8 weeks. Primary outcome was the disease flare rate

defined as worsening of disease activity using DAS 28. Secondary outcome was fatigue measured by Functional

Assessment of Chronic Illness Therapy-Fatigue subscale (FACIT-F, score range is 0-52 with lower scores representing

greater fatigue). Those were evaluated at baseline, 8 and 16 weeks. The changes of outcome were compared between KRG

and placebo period using paired t-test.

Results: Among total patients, 70 patients completed study periods. Female patients whose mean age was 51.9 years

were enrolled. The mean of FACIT-F at baseline was 22.0±6.6. Seventy eight patients (97.5%) have low or moderate dis-

ease activity (DAS28 mean 3.5±1.0). The disease fare rate was same as 3.7% (n=3) in both periods. Improvement of fa-

tigue was better in KRG group compared with placebo group (2.66±6.37 vs. 1.36±6.14 in FACIT-F, p=0.31), although

there were no statistical significance. These results were consistent in subgroup analyses for patients more than

pill-count 80%.

Conclusions: KRG did not associated with disease flare in RA patients. Fatigue tends to be improved with KRG, but

the differences were not statistically significant. Further study with increasing sample size will be required to adequately

address the effectiveness of KRG on improvement in fatigue of RA patients.

O-20-13


S73

Remission of Rheumatoid Arthritis Judged by 2 Criteria

Sung Yeon Lee1, Kyeong Min Son2, Young Il Seo1, Hyun Ah Kim1

1Division of Rheumatology, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, 2Division of Rheumatology, Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Korea

Objectives: To investigate the remission rate of rheumatoid arthritis (RA) and find out the clinical factors that are asso-

ciated with attaining remission measured by Disease Activity Score in 28 joints (DAS28) and ACR/EULAR Boolean

criteria.

Methods: Every RA patient, who first visited rheumatology clinics of Hallym University Sacred Heart Hospital from

August 2010 to December 2013, and started DMARD treatment, was evaluated with DAS28 every 3months. We calcu-

lated remission rate using DAS28 and Boolean criteria after 6 months of treatment. Logistic regression analyses was used

to identify clinical factors that were associated with remission.

Results: A total of 285 patients were included. The remission rates of RA were 26.3% in DAS28 and 8.1% in Boolean

criteria. Patients who achieved DAS28 remission were significantly younger age, and had lower tender joint count (TJC),

swollen joint count (SJC), baseline DAS28, and ESR compared to those who did not. Patients who achieved Boolean re-

mission had shorter disease duration, lower TJC, SJC, baseline DAS28, CRP, and were treated with lower starting dose

of glucocorticoids. Multivariate analysis showed lower starting dose of glucocorticoids as an independent predictor of

Boolean remission. Among 75 patients with DAS28 remission, 25.3% achieved Boolean remission. Patients failing

Boolean remission criteria despite achieving DAS28 remission had significantly longer disease duration compared to

those who achieved remission by both criteria.

Conclusion: The remission rate of RA in Boolean criteria was much lower than DAS28. Longer disease duration was

significantly associated with failing Boolean remission criteria despite achieving DAS28 remission.

O-20-14

(2010. 1. 1∼2010. 12. 31)


Free Paper Session: Systemic Lupus Erythematosus,

Sjogren's Syndrome Basic Aspects


S77

A Selective JAK1 Inhibitor, Filgotinib Ameliorates Sjogren's Syndrome in Non Obese Diabetes Mice Via

Suppression of BAFF and Chemokine Production of Salivary Gland Epithelial Cells

Jennifer Lee1, Jaeseon Lee2, Seung-Ye Baek2, Seung-Ki Kwok1, Mi-La Cho2, Sung-Hwan Park1

1Division of Rheumatology, Department of Internal Medicine, School of Medicine, The Catholic University of Korea, Seoul St. Mary’s Hospital, Seoul, 2Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, Korea

Background: Interferon (IFN) signatures are upregulated in patients with primary Sjogren’s syndrome (pSS) and inter-

ferons are considered to play a pathogenic role in pSS. Therefore, Janus kinase (JAK) which mediates interferon signaling

pathway may be a good therapeutic target.

Objective: To investigate whether a selective JAK1 inhibitor, filgotinib would ameliorate disease-related parameters in

non-obese diabetic (NOD) mice, an animal model SS.

Methods: Filgotinib (1.5 mg/kg) or vehicle (saline) was intraperitoneally injected three times per week from 8 weeks

after birth. Salivary flow rate (SFR) was addressed on 8, 12, 16 and 20 weeks. Histologic analysis was performed on 20

weeks. The effect of filgotinib on the expressions of B cell activating factor (BAFF) and chemokines (CXCL10 [IP-10],

CXCL3 [fractalkine], CCL-2 [MCP-1]) in human salivary gland epithelial cell (SGEC) line or primary epithelial cells of

patients with pSS was determined in vitro.

Results: The SFR of NOD mice in both groups decreased over time. Lymphocytic infiltration increased over time, espe-

cially marked B cell infiltration was noted. SFRs of filgotinib-treated mice were greater than those of controls. On histo-

logic evaluation, lymphocytic infiltration of salivary gland was markedly reduced in the mice treated with filgotinib.

Similarly, the expression of IFN-γ and TNF-α was lower in the salivary gland of filgotinib-treated mice. IFN-α treat-

ment induced BAFF and chemokine production both in SGECs and primary epithelial cells obtained from pSS patients,

which was abrogated by filgotinib treatment. Filgotinib suppressed STAT1 phosphorylation and the expression of IFN

signature genes in these cells.

Conclusion: Filgotinib inhibits IFN signaling and suppresses BAFF and chemokine expression of salivary gland epi-

thelial cells, which suppresses lymphocytic infiltration of salivary glands and alleviates the decrease of SFRs of NOD

mice. JAK1 inhibition may be a novel therapeutic approach for SS.

O-20-15


S78

Exosomes from Patients with Active Systemic Lupus Erythematosus Induce a Strong Inflammatory Response

Joo Youn Lee1, Jin Kyun Park1,2, Eun Young Lee2, Eun Bong Lee2, Yeong Wook Song1,2

1Department of Molecular Medicine and Biopharmaceutical Sciences, Seoul National University, Seoul, 2Division of Rheumatology, Department of Internal Medicine, Seoul National University, Seoul, Korea

Background: Exosomes are 60-150 nm membrane vesicles that are secreted by various cells into surrounding body flu-

ids including blood and urine. As vehicles for intercellular communication, they are involved in immune cell activation.

To date, the role of exosomes in pathogenesis of systemic lupus erythematosus (SLE) has not been fully elucidated.

Objectives: This study was aimed to investigate as to whether exosome formation is increased and whether they effec-

tively contribute to proinflammatory cytokine response in patients with SLE.

Methods: Serum samples from SLE patients, rheumatoid arthritis (RA) patients and healthy controls were obtained

at Seoul National University Hospital. Exosomes were isolated from sera using ExoQuick and quantified using EXOCET.

Healthy peripheral blood mononuclear cells (PBMCs) were stimulated with exosomes from SLE patients, RA patients or

healthy controls. After 24 hours, production of interferon (IFN)-α, interleukin (IL)-1β, IL-6, and tumor necrosis factor

(TNF)-α were measured using ELISA. Correlation between SLE disease activity index (SLEDAI) and exosome levels was

assessed by Spearman correlation.

Result: The purified exosomes were 60-150nm in size and had a membrane bilayer on electron microscopy. Exosomes

from SLE induced healthy PBMCs to produce high levels of IFN-α, IL-1β, IL-6, and TNF-α, whereas exosomes derived

from RA patients or healthy controls did not. Exosome-depleted SLE serum and SLE exosomes that were mechanically

disrupted fail to elicit any significant proinflammatory cytokine production. The serum levels of exosomes were sig-

nificantly higher in SLE patients than healthy controls and their levels correlated with SLEDAI in patients with SLE.

Conclusion: These data suggest that exosomes are generated and contribute to proinflammatory response in patients

with SLE. Exosomes might serve as a novel biomarker of disease activity. Treatment targeting exosome might offer a new

therapeutic option.

O-20-16


S79

Urinary Immunoglobulin Binding Protein-1 as a Biomarker Related with Lupus Nephritis Activity

Eun-Ju Lee1,2, Seokchan Hong2, Bin Yoo2, Chang-Keun Lee2, Yong-Gil Kim2

1Asan Institute for Life Science, Asan Medical Center, Seoul, 2Department of Rheumatology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea

Background/Purpose: Systemic lupus erythematous (SLE) is a multisystem autoimmune inflammatory disease. Lupus

nephritis (LN) is one of the most serious complications in patients with SLE. Immunoglobulin binding protein-1 (IGBP1)

originally was discovered as a phosphoprotein associated with the immunoglobulin receptor in B cells. The objective of

the present study was to determine urinary IGBP1 levels in LN patients and identify any correlations between urinary

IGBP1 levels with other clinical variables and renal pathology.

Methods: The levels of IGBP1 were measured in urine of SLE patients with (n=40) or without (n=30) nephritis, and

healthy subjects (n=18). Correlation analyses between urinary IGBP1 levels and the diseases-related variables including

c-reactive protein (CRP), erythrocyte sedimentation rate (ESR), anti-double-stranded DNA antibody (anti-dsDNA), and

SLE Disease Activity Index (SLEDAI) were examined. In addition, we performed correlation analyses of urinary IGBP1

levels with activity index score or chronicity index score in renal biopsy samples. To define IGBP1 expression in renal

pathologies, immunohistochemical stainings were performed.

Results: Urinary levels of IGBP1 were significantly higher in LN than in SLE without nephritis and healthy individuals.

Among the diseases-related variables, SLEDAI scores, anti-dsDNA, and C3 were significantly correlated with the levels

of urinary IGBP1. Further, urinary IGBP1 levels represented a significant positive association with activity index score

(p=0.0072). In immunohistochemical staining results, IGBP1 was expressed mainly in tubules, especially in class III and

IV.

Conclusion: This study demonstrates that the levels of urinary IGBP1 were significantly higher in LN patients and were

correlated with disease activity and activity index score of renal pathology. Therefore, IGBP1 might be a valuable tool for

determining high disease activity in LN patients.

O-20-17


S80

Fn14-Fc Suppresses Germinal Center Formation and Pathogenic B Cells in a Lupus Mouse Model Via Inhibition of the TWEAK/Fn14 Pathway

Hong-Ki Min1,2*, Sung-Min Kim1*, Jin-Sil Park1, Jae-Kyeong Byun1, Jennifer Lee1,2, Seung-Ki Kwok1,2, Young-Woo Park3, Mi-La Cho1§, Sung-Hwan Park1,2§

1Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, 2Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul,

3Integrative Omics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea

Background: Systemic lupus erythematosus (SLE) is an autoimmune-mediated chronic inflammatory disease. Half of

patients with SLE suffer from lupus nephritis, which is major cause of death in SLE. TNF-like weak inducer of apoptosis

(TWEAK)/fibroblast growth factor-inducible 14 (Fn14) interactions mediate inflammatory responses that are linked to

the pathogenesis of lupus nephritis. Blocking of the TWEAK/Fn14 pathway by Fn14-Fc was performed in a SLE mouse

model and the likely therapeutic mechanisms were investigated.

Methods: To investigate the impact of TWEAK on B-cell differentiation in SLE, the levels of AID, Blimp-1, and IRF4

messenger RNA were measured in CD19+ B cells extracted from the spleens of sanroque mice and cultured with

TWEAK. To identify the therapeutic effects of Fn14-Fc in SLE, sanroque mice were treated with Fn14-Fc or a control-Fc

for 3 weeks. Immunoglobulin (Ig) G, IgG1, IgG2a, and anti-dsDNA antibody (Ab) levels were measured in the sera of

each group. Spleens from each group were stained with antibodies against CD4, B220, GL-7, CD138, and PD-1. Kidneys

were stained with hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS).

Results: Administration of TWEAK increased the mRNA levels of AID, Blimp-1, and IRF4. Treatment with Fn14-Fc

suppressed levels of IgG, IgG1, IgG2a, and anti-dsDNA Ab in sera and reduced numbers of B-, plasma-, and follicular

helper T-cells (Tfh) in spleens of sanroque mice. In addition, renal protective effects of Fn14-Fc were shown.

Conclusion: Fn14-Fc had beneficial effects in a SLE mouse model by repressing B cells, plasma cells, Tfh, and renal

damage. This suggested that Fn14-Fc represents a potential therapeutic agent for SLE.

O-20-18

(2010. 1. 1∼2010. 12. 31)


Free Paper Session: Osteoarthritis


S83

DICAM Promote Proliferation and Hypertrophic Differentiation of Chondrocyte through

Indian Hedgehog Signaling of Primary Cilia

Seung-woo Han1,2, Min-Su Han1, Hye-Ri Park1, Eun-Ju Lee1, Ji-Ae Jang1, Gun-Woo Kim1,2, Youn-Kwan Jung1

1Laboratory for Arthritis and Bone Biology, Fatima Research Institute, 2Department of Internal Medicine, Daegu Fatima Hospital, Daegu, Korea

Background and Objectives: DICAM (dual Ig domain containing cell adhesion molecule) was originally cloned from

human chondrocyte cell-line, HCS-2/8 cells, but the role during endochondral bone formation and osteoarthritis has not

been elucidated.

Methods: Primary chondrocytes and tibia were isolated from limbs of C57BL/6 embryo (E15.5) and used in vitro study.

Cartilage-specific DICAM transgenic (Col2-DICAM-Tg) mice was constructed and the phenotype of E15.5 long bone was

compared with their wild type-littermates.

Results: DICAM mainly expressed in resting and proliferating chondrocytes in growth plate and it was increased by

Pthrp and BMP2 in primary chondrocytes. Gain-of function study with Col2-DICAM-Tg revealed that DICAM increased

length of long bones. Col2-DICAM-Tg showed an increased expression of chondrogenic, Col2a1 and proliferating mark-

er, PCNA in immunohistochemical analysis. In addition, early and late hypertrophic chondrocyte marker, Col10a1 and

MMP13, respectively, also increased in Col2-DICAM-Tg compared to wild-type. To elucidate a molecular mechanism of

DICAM, we checked the major signaling targets in chondrogenesis, which showed an increased expression of HHIP and

Zfp521, the target molecule of Ihh and Pthrp signaling, respectively. Other Ihh signaling molecules such as Ptch1, Gli1,

Gli2, Gli3 and Ihh itself were also increased by DICAM overexpression in primary chondrocytes. Mechanistically, DICAM

was co-localized with primary cilia of chondrocytes and increased a number of primary cilia and their adaptor molecule,

IFT88. Knock-down of IFT88 and hedgehog signaling antagonist, cyclopamine, attenuated the DICAM-mediated in-

crease of length in primary tibia organ culture.

Conclusion: DICAM was colocalized with primary cilia in resting and primary chondrocytes and modulated Ihh signal-

ing, which was responsible for a chondocyte proliferation and hypertrophic differentiation during endochodral bone

formation.

O-20-19


S84

Fibronectin Fragment Suppresses Xylosyltransferase-1 Expression through Modulating Sp1 and Sp3 Expression

Via MAPK, AP-1, and NF-κB Signaling Pathways

Mi Hyun Lee1, Hyun Sook Hwang2, Hyun Ah Kim3

1Division of Rheumatology, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Kyunggi, 2Institute for Skeletal Aging, Hallym University, Chunchon, Korea

Background: Xylosyltransferase-1 (XT-1) is an essential anabolic enzyme in glycosaminoglycan chain synthesis. The

effect of fibronectin fragments (FN-fs), known as damage-associated molecular pattern (DAMP) molecules, on cartilage

metabolism was poorly characterized.

Objective: In this study we examined 29-kDa amino-terminal fibronectin fragment (29-kDa FN-f)-mediated XT-1 ex-

pression mechanism and its signaling pathway, determining the role of 29-kDa FN-f in cartilage matrix synthesis.

Methods: The relative levels of mRNA and protein for XT-1 and aggrecan were analyzed by real-time quantitative PCR

and immunoblotting. siRNAs were used to knock down Toll-like receptor (TLR)-2, Sp1, and Sp3. The signaling pathways

related with XT-1 expression was investigated by immunoblotting using pharmacological inhibitors

Results: The expression of aggrecan and XT-1 was significantly lower in human osteoarthritis cartilage compared to

normal cartilage. XT-1 expression in cultured primary articluar chondrocytes showed a periodic oscillation in both

mRNA and protein level. 29-kDa FN-f significantly suppressed the mRNA and protein levels of XT-1 as well as caused

the decreased Sp1 expression and increased Sp3 expression. Knockdown and overexpression experiments revealed that

29-kDa FN-f suppressed XT-1 expression through modulation of Sp1 and SP3 expression. Knockdown of TLR-2 using

siRNA revealed that the decrease of XT-1 expression by 29-kDa FN-f is mediated by TLR-2 signaling pathway. Inhibition

of MAPK and NF-κB signaling pathways restored 29-kDa FN-f-inhibited XT-1 expression. In addition, 29-kDa FN-f sup-

presses XT-1 expression through inducing translocation of phosphorylated the c-jun and c-fos into nucleus and sub-

sequently activating AP-1 signaling pathway.

Conclusion: These results demonstrated that 29-kDa FN-f plays a detrimental role in the regulation of cartilage ex-

tracellular matrix formation, including XT-1 expression, via the MAPK, AP-1, and NF-κB signaling pathways

O-20-20


S85

Metabolic and Inflammatory Links to Rotator Cuff Tear in Hand Osteoarthritis

Young Sun Suh1, Yun-Hong Cheon2, Hyun-Ok Kim1, Rock-Bum Kim3, Ki Soo Park3, Hyung Bin Park4, Jae-Bum Na5, Sang-Il Lee2

1Division of Rheumatology, Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Changwon, 2Division of Rheumatology, Department of Internal Medicine, 3Preventive Medicine, 4Orthopedic Surgery, and 5Radiology,

Gyeongsang National University School of Medicine, Jinju, Korea

Background: Rotator cuff tear (RCT) and hand osteoarthritis (HOA) are commonly accompanied because they share

a similar pathogenesis. However, there was no previous study investigating the relationship between RCT and HOA.

Objectives: To estimate the prevalence of RCT and factors associated with development of RCT in patients with HOA.

Methods: We enrolled 1150 inhabitants in Gyeongnam province in Korea from June 2013 to December 2015. Physical

examinations of upper extremities, plain radiography of hands and magnetic resonance imaging (MRI) of shoulders were

performed in all participants. Serum levels of high sensitive C reactive protein (hsCRP) and high density lipoprotein

(HDL) were checked. RCT was diagnosed by clinical examination and MRI findings. Diagnosis of HOA was made by the

1990 American College of Rheumatology classification criteria.

Results: The prevalence of RCT was higher in participants with HOA group (192/307, 62.5%) than those without HOA

(410/827, 49.5%, p<0.001). Among 307 with HOA, people with RCT were older (62.69±7.04 vs. 59.11±7.69, p<0.001)

and showed higher hsCRP (1.51±3.78 vs. 0.67±0.70, p=0.004) and lower HDL levels (55.66±15.46 vs. 60.48±12.45,

p=0.003) compared to those without RCT. Multiple logistic regression analysis showed significant associations of age

(odds ratio [OR] 1.1; 95% confidence interval [CI] 1.021-1.098), serum levels of hsCRP (OR 1.4, CI 1.044-1.795), and

low HDL (male <40 mg/dL, female <50 mg/dL) (OR 2.1, CI 1.142-3.978) with RCT in HOA group. Stratified by age,

the low HDL (OR 3.8, C.I 1.310-10.937) and high hsCRP over 0.6 mg/L (OR 2.5, C.I 1.091-5.571) were significantly as-

sociated with RCT among participants under 60 years with HOA.

Conclusions: The prevalence of RCT is high and age and serum levels of hsCRP and HDL have predictive roles in the

development of RCT in HOA patients.

O-20-21


S86

Association between Grip Strength and Hand and Knee Radiographic Osteoarthritis in Older Adults:

Data from the Dong-gu Study

Lihui Wen1, Ji-Hyoun Kang1, Yi-Rang Yim1, Ji-Eun Kim1, Jeong-Won Lee1, Kyung-Eun Lee1, Dong-Jin Park1, Tae-Jong Kim1, Yong-Wook Park1, Sun-Seog Kweon2,3,

Young-Hoon Lee4, Yong-Woon Yun5, Min-Ho Shin2, Shin-Seok Lee1

1Department of Rheumatology, Chonnam National University Medical School & Hospital, Gwangju, 2Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, 3Jeonnam Regional Cancer Center, Chonnam National University Hwasun Hospital,

4Department of Preventive Medicine & Institute of Wonkwang Medical Science, Wonkwang University College of Medicine, Iksan, 5Gwangju-Jeonnam Regional Cardiocerebrovascular Center, Chonnam National University Hospital, Gwangju, Korea.

Objective: We assessed whether grip strength was related to various types of radiographic damage in older adults with

osteoarthritis (OA).

Methods: Data from 2,251 subjects enrolled in the Dong-gu study, who had no hand joint pain, were analyzed to inves-

tigate the relationship between grip strength and OA. Hand grip strength was measured using a hand-held dynamometer,

and radiographs of the hand and knee were scored according to a semi-quantitative grading system. Multiple linear re-

gressions were used to explore associations between grip strength and radiographic features of OA.

Results: Grip strength in men and women was negatively related to hand (both p<0.001) and knee (men, p<0.001;

women, p=0.010) OA after adjusting for confounders. Hand (men, p<0.001; women, p=0.001) and knee (both

p<0.001) joint space narrowing (JSN) showed the strongest associations with low grip strength, regardless of sex.

Moreover, the severity of hand osteophytes in women (p=0.001), knee osteophytes in men (p=0.006), hand malalign-

ment (men, p=0.008; women, p=0.041), and subchondral cysts (men, p<0.001; women, p=0.007) was correlated with

low grip strength in both sexes.

Conclusions: Among subjects without hand joint pain, low grip strength was associated significantly with hand and

knee radiographic OA, regardless of sex. Among all types of OA radiographic damage, low grip strength showed the stron-

gest association with JSN.

O-20-22


S87

The Prevalence and Risk Factor of Knee Pain in Advacned Knee Osteoarthritis

Kyeong Min Son1, Dong-Hyun Kim2, MyungHee Cho Paik3, Dae Gyu Jang3, Hyun Ah Kim1

1Department of Internal Medicine, Hallym University Colleage of Medicine, 2Deparment of Social and Preventive Medicine, Hallym University College of Medicine,³Department of Statistics, Seoul National University

Background: Although osteoarthritis (OA) is predominantly considered as a disease of cartilage, articular cartilage is

an aneural tissue, and there is a consensus that the association between knee radiographic OA and knee pain is modest.

Objectives: To investigate the prevalence of asymptomatic subjects with advanced knee OA, we examined databases

obtained from 2 Korean community residents.

Methods: Subjects included were from Hallym Aging Study (HAS) or from the Korean National Health and Nutrition

Examination Survey (KNHANES, year 2010-2012). Participants in each study were asked knee-specific questions regard-

ing presence of knee pain. Each knee was graded for overall evidence of radiographic OA using the K-L grade. Advanced

knee OA was defined as K-L grade 4. Clinical factors associated with the presence of knee pain were evaluated with multi-

varitate logistic regression analysis.

Results: Included were 504 subjects from HAS and 8679 from KNHANES. Two hundred twenty five subjects (44.3%)

did not report any pain despite having K-L grade 4 OA. After multivariate association, female and osteoporosis was sig-

nificantly associated with the presence of knee pain. Advanced OA Subjects without knee pain had functional status eval-

uated with WOMAC and chair stand not different from that of non-OA subjects. General physical health, assessed with

the short-form (SF-12) method was not different between advanced OA subjects without knee pain and non-OA subjects

except physical functioning. MRI findings such as summary cartilage score, bone marrow lesion score, synovitis and effu-

sion of advanced OA subjects without knee pain was not different from those of advanced OA subjects with knee pain.

Conclusion: Our community study showed that a majority of subjects with K-L grade 4 OA was asymptomatic. The

guidance of therapeutic decision merely based on imaging study as well as treatment option focusing solely on cartilage

engineering should be viewed with caution.

O-20-23

(2010. 1. 1∼2010. 12. 31)


Free Paper Session: Spondylarthropathies,

Epidemiology


S91

The Incidence of Herpes Zoster Infection in Patients with Ankylosing Spondylitis: Analysis from Korean National

Health Insurance Service-Cohort Sample Database

Doo-Ho Lim1, Byeongzu Ghang2, Seokchan Hong2, Yong-Gil Kim2, Chang-Keun Lee2, Bin Yoo2

1Division of Rheumatology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, 2Division of Rheumatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Background: Herpes zoster (HZ) infection occurs more commonly in patients with underlying autoimmune disease,

partially due to immunosuppressive treatment. However, little is known about the incidence of HZ in patients with anky-

losing spondylitis (AS), especially who were treated with conventional disease modifying anti-rheumatic drugs

(cDMARDs) or TNF inhibitors.

Objectives: The aims of our study were to investigate the incidence of HZ in AS patients and to determine whether use

of cDMARDs or TNF inhibitors could increase the risk of HZ infection in AS patients.

Methods: We used database of the Korean National Health Insurance Service?Cohort Sample (1,025,340 individuals)

from 2002 to 2013. We evaluated HZ incidence among three groups (non-DMARD users, cDMARDs users and TNF in-

hibitor users) based on drug exposure episodes.

Results: Among 1,079 patients with AS, we identified 54 HZ infections. Crude incidence rates were 11.0 per 1000 pa-

tient-years (95% CI, 8.2-14.3) in all AS patients; 9.1 (95% CI, 6.2-12.8) in non-DMARD users, 16.7 (95% CI, 9.1-28.0)

in cDMARDs users and 14.1 (95% CI, 6.1-27.8) in TNF inhibitor users, respectively. Adjusted hazard ratio (HR) of HZ

infection was higher in cDMARDs users and TNF inhibitor users than in non-DMARD users. In subgroup analysis, TNF

inhibitor increased the risk of HZ infection more significantly in female (adjusted HR=8.01; 95% CI, 1.97-32.54) and pa-

tients older than 50-yr (adjusted HR=7.29; 95% CI, 1.88-28.21), but not in patients exposed to baseline corticosteroid

(95% CI, 0.53-32.84) compared to non-DMARD users.

Conclusions: The incidence of HZ in AS patients was 11.0 per 1000 patient-years which is similar to the previously re-

ported incidence in general Korean population. cDMARDs or TNF inhibitors increased the risk of HZ infection in AS pa-

tients, especially in female and older patients, which can be considered as target of HZ vaccination in AS population.

O-20-24


S92

Utilization of the PEST Questionnaire to Detect Psoriatic Arthritis in Clinical Practice:

Data from the VALidation of psORiatic Arthritis Screening Tool for Korean Psoriasis Patients (VALOR) Study

You-Jung Ha1, So Yeon Cho2, Sang-Heon Lee3, Yong Beom Choe4, Tae-Hwan Kim5, Joo Yeon Ko6, Sung Jae Choi7, Il-Hwan Kim8, Sang Woong Youn9, Kichul Shin10

1Divsion of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, 2Department of Dermatology, SMG-SNU Boramae Medical Center, 3Department of Dermatology, Konkuk University School of Medicine, 4Division of Rheumatology,

Department of Internal Medicine, Konkuk University School of Medicine, 5Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, 6Department of Dermatology, Hanyang University College of Medicine, 7Division of Rheumatology, Department of Internal Medicine, Korea University Ansan Hospital, 8Department of Dermatology, Korea University Ansan Hospital, 9Department of Dermatology, Seoul

National University Bundang Hospital, 10Division of Rheumatology, Department of Internal Medicine, SMG-SNU Boramae Medical Center

Background: Several questionnaires have been developed to help identify psoriatic arthritis (PsA) among psoriasis

(PsO) patients, but there is no screening tool yet tested through joint efforts by Dermatologists and Rheumatologists in

Korea. The PsO Epidemiology Screening Test (PEST) is a simple questionnaire that could be used without assistance.

Objectives: This study aimed to investigate the utility and validation of PEST for screening PsA in Korean PsO patients.

Methods: The PEST, consisted of 5 questions, was translated into Korean and then back-translated to English for

comparison. This form was tested on PsO patients visiting the Dermatology clinic at 5 hospitals in urban areas. Patients

who checked ‘yes' to 2 or more questions were referred to Rheumatology for further evaluation. Patients meeting the

CASAPR criteria were then confirmed to have PsA.

Results: Data of 191 PsO patients from 5 centers were analyzed. The mean age was 45.1 years, and male/female ratio

was 1.27. Among the 41 (21.5%) patients who checked 'yes' to 2 or more questions, 35 patients were eventually assessed

by a Rheumatologist. Of these subjects, 16 (45.7%) patients were diagnosed as PsA. When comparing baseline character-

istics between PsA and PsO-only patients, the proportion of female in the PsA group was significantly higher than that

the PsO-only group (68.8 vs. 41.4%, p=0.035). BSA of PsO and the % of nail involvement were also higher in PsA pa-

tients, but did not reach statistical significance. Using the known PEST cut-off score of 3, its specificity increased to

93.5%, but sensitivity dropped to 50%.

Conclusion: This study supports that PsO patients with musculoskeletal symptoms should be carefully evaluated for

PsA especially when patients are female, and have nail involvement and higher BSA of PsO. The Korean version of PEST

is a convenient tool for screening PsA, yet its peformance and utility in our region with a different PsA population need

to be further investigated.

O-20-25


S93

Increased 18F-fluoride Uptake Lesions at Vertebral Corners on Positron Emission Tomography Predict New

Syndesmophytes Development in Ankylosing Spondylitis

Seung-Geun Lee, Eun-Kyoung Park, Ji-Heh Park

Division of Rheumatology, Department of Internal Medicine, Pusan National University Hospital, Korea

Background: 18F-fluoride uptake on positron emission tomography (PET) represents osteoblastic activity. But, longi-

tudinal studies that investigated the association between increased 18F-fluoride uptake lesions and future syndesmo-

phytes formation are lacking.

Objectives: To demonstrate that increased 18F-fluoride uptake lesions on PET predict the development of new

syndesmophytes.

Methods: In 12 patients with AS, 18F-fluoride PET-MRI (Philips Healthcare, Cleveland, OH, USA) was performed at

baseline and radiography was performed at baseline and 2 years. We recorded 18F-fluoride uptake lesions on PET, acute

(type A) and advanced (type B) corner inflammatory lesions (CILs) and fat lesions on MRI and syndesmophytes on

radiography. An increased 18F-fluoride uptake lesion was defined as an uptake greater than the uptake in the adjacent

normal vertebral body (Fig. 1).

Results: Of 231 anterior vertebral corners without syndesmophyte at baseline, 13 type A CILs (5.5%), 2 type B CILs

(0.9%) and 20 fat lesions (8.7%) on MRI and 6 increased fluoride uptake lesions (2.6%) on PET were observed. After 2

years, 16 new syndesmophytes (6.9%) in 8 AS patients (66.7%) occurred. New syndesmophytes developed significantly

more frequently in anterior vertebral corners with in-

creased 18F-fluoride uptake lesions (50%) or fat le-

sions (25%) at baseline, as compared with those

without either feature (5.8 % and 5.2%, respective-

ly). After adjusting within-patient correlation, base-

line increased 18F-fluoride uptake lesion signifi-

cantly predicted the development of new syndesmo-

phytes (OR=20.6 95% CI=2.7-156.1, p=0.003). Fat

lesions were also associated with new syndesmo-

phytes development, but this association was not ob-

served in CILs.

Conclusions: Our findings indicate that increased

18F-fluoride uptake lesions can predict future new

syndesmophytes formation of AS.

O-20-26


S94

Korean Rheumatology Workforce from 1992 to 2015: Rapid Advance, being on the Rise

of Regional Concentration, in Metropolitan

Chan Uk Lee, Sung-Hoon Park, Hwajeong Lee, Ji-Na Kim, Ji-Won Kim, Seong-Kyu Kim, Jung-Yoon Choe

Medicine Catholic University of Daegu School of Medicine, Korea

Objective: Rheumatology of Korea has been rapidly advanced in a brief span of 36 years since the subspecialty board

certification program was established in 1992. The objectives of this investigation is to analyze the distribution of rheu-

matology practices in Korean in order to better understand the appropriate supply of the workforce.

Methods: Using a membership list of KCR (Korean College of Rheumatology), information of practicing rheumatolo-

gist was obtained. We mapped the ratios of rheumatologist to population and patient with rheumatologic disease, using

data of Statistics Korea and 2015 HIRA (Health Insurance Review & Assessment service).

Results: In 16 administrative districts of Korea, in 2015, there were 311 practicing rheumatologist in a list of member

of KCR. There were 218 members practicing in metropolitans and 93 members in provinces. In whole country, mean

number of rheumatologist per 100,000 populations was 0.60 and was 0.33 in provinces but was 0.92 in metropolitans.

In comparison that number of internal medicine specialist in 2014, difference of between provinces and metropolitans

was 1.5 times in internal medicine specialist but was 2.7 times in rheumatologist. And number of rheumatologist per pa-

tients that be practiced from 7 groups according to 2015 HIRA data, were 17.21(per 100,000 patients) in metropolitans

but were 6.57 in provinces.

Conclusion: Because of uneven distribution of rheumatologist, some patients with chronic rheumatic conditions likely

have limited access to rheumatology care. So newly policy based approach need to be taken into account to alleviate a

disparity.

Keywords: Rheumatologist, Distribution, KCR, Concenturation

O-20-27

(2010. 1. 1∼2010. 12. 31)


Free Paper Session: Behcet's Disease,

Myositis


S97

Serum CXCL10 Levels are Associated with Clinical Manifestations and Disease Activity in Behçet’s Disease:

A Prospective Follow-up Study

Sang Jin Lee1,2, Eun Ha Kang3, Byoong Yong Choi4, Shin Eui Kang2, Jin Kyun Park1,2, Eun Young Lee1, Eun Bong Lee1, Yeong Wook Song1,2

1Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, 2Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine, Medical Research Center,

Seoul National University, 3Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, 4Division of Rheumatology, Department of Internal Medicine, Seoul Medical Center, Seoul, Korea

Background: It remains to be investigated which chemokines are important in Behçet’s disease (BD). The objective of

this study was to investigate serum levels of CXC chemokines in BD patients and their association with clinical manifes-

tations and disease activity.

Methods: Blood samples were collected from 109 BD patients and 36 age- and sex-matched healthy controls (HCs).

Twenty-two follow-up blood samples were collected in BD patients. Serum CXC chemokines were assayed for neutrophil

chemoattractants (CXCL1, CXCL8, CXCL9, CXCL10, CXCL12, CXCL13 and CXCL16) using a multiplex assay. Cell sur-

face maker expression (CD3, CD4 and CXC chemokine receptor 3 (CXCR3)) in peripheral blood mononuclear cells

(PBMCs) was investigated by flow cytometry. Clinical features including disease activity, laboratory tests and current

medication were evaluated at the time of blood collection. CXCR3 and CD45 expression in skin and intestinal lesions

from BD patients and HCs was assessed via immunohistochemistry.

Results: Serum levels of CXCL8, CXCL10 and CXCL12 were significantly higher in BD patients than in HCs. Serum

CXCL10 levels were correlated with disease activity in terms of both Behçet’s Disease Current Activity Form (BDCAF)

and Behçet’s Syndrome Activity Score (BSAS) (rho=0.336, p<0.001 and rho=0.253, p=0.009, respectively). In fol-

low-up BD patients, changes in serum CXCL10 levels were correlated with those of BDCAF. CXCR3 expression was sig-

nificantly increased in CD3-positive cells versus CD3-negative cells in PBMCs from both BD patients and HCs.

Percentages of CXCR3 expression in CD3-positive cells were inversely correlated with serum CXCL10 levels in BD

patients. By immunohistochem-

istry, the number of CXCR3-

positive mononuclear cells was

higher in skin lesions of BD pa-

tients than in those of HCs.

Conclusions: These results

suggest that the CXCL10/CXCR3

axis contributes to the patho-

genesis of BD, particularly mu-

cocutaneous lesions.

O-20-28


S98

Optimal Surgical Method for Aortic Regurgitation in Behcet Disease

Byeongzu Ghang1, Suk Jung Choo2, Ohchan Kwon1, Wook Jang Seo3, Seokchan Hong1, Yong-Gil Kim1, Chang-Keun Lee1, Bin Yoo1

Division of 1Rheumatology, Department of Internal Medicine, and 2Thoracic and Cardiovascular Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 3Seoul Veterans Hospital, Seoul, Korea

Background/Objectives: Aortic regurgitation (AR) in Behcet disease is a rare but very fatal condition. Many patients

required a second or third operation after simple aortic valve replacement (AVR) as a result of prosthetic valve

dehiscence. Recently, a few case series have been published aortic root replacement (ARR) have shown favorable out-

come but they have not suggested yet as an effective surgical method because of lack of evidence. Thus, we compare

long-term outcome between isolated AVR and ARR after first operation.

Methods: From January 1996 through December 2015, 31 patients with AR caused by Behcet disease have been surgi-

cally treated. AVR was performed in 14 cases and ARR in 17 cases. According to the definition of the event; aortic

valve/graft problem, infective endocarditis, cerebral infarction cased by thromboembolism or re-operation of aortic valve;

we compared events after first operation between two groups. The duration of follow-up was 164.7±63.3 months (AVR

group) and 74.4±55.4 months (ARR group).

Results: In the 14 patients with isolated AVR, events occurred in 12 patients (39.3±43.8 months after operation) and

re-operations were performed in 17 cases. In the 17 patients with ARR, events occurred in 6 patients (56.2±52.4 months

after operation), necessitating re-operations in 5 cases (AVR group vs. ARR group; p=0.006). Kaplan-Meier curves dis-

played higher event free rate in ARR group compared to AVR group (p=0.027). Overall mortality was 12.9% (4 of 14 pa-

tients in AVR group, 0 of 17 patients in ARR group, p=0.032). As post operational medications, steroid was used more

frequently in patients with ARR than AVR group (4 patients vs 15 patients, p=0.028).

Conclusion: In patients with AR related with Behcet disease, the rate of event and mortality was lower in patients with

ARR compared to those with isolated AVR.

O-20-29


S99

Major Comorbidities of Idiopathic Inflammatory Myositis Affecting Survival and Functional Impairment:

A Population-based Study Using 11 Years of Follow Up from the National Health Insurance in Korea

Jeong Seok Lee1, Min Jung Kim1, Hee Young Lee2, So Yeon Ahn3, Yeong Wook Song1, Eun Bong Lee1, Eun Young Lee1, Yun Jong Lee4, Eun Ha Kang4

1Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Seoul, 2Center for Preventive Medicine and Public health, Seoul National University Bundang Hospital, Seongnam,

3Medical Research Collaborating Center, Seoul National University Bundang Hospital, Seongnam, 4Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.

Background: Patients with idiopathic inflammatory myositis (IIM) suffer from comorbidities such as interstitial lung

disease (ILD), cancer, and infections related to immunosuppressive agents.

Objectives: To evaluate 1) incidence rate ratio (IRRs) of major comorbidities in IIM compared to non-IIM Koreans, and

2) impact of the comorbidities on survival and functional impairment.

Methods: A retrospective cohort study was performed using the 2002-2013 National Health Insurance Service (NHIS)

database of weighted probability sampled one million cohort. IIM was identified by at least two visits to the tertiary hospi-

tals under ICD9 code of IIM. Age- and sex-matched twenty subjects per patient were included as the unexposed.

Results: Ninety-one patients were newly diagnosed as IIM from 2003 to 2013. Most patients (>90%) defined as such

were found to have muscle biopsy, electromyogram, or multiple laboratory examinations on muscle enzymes. Their in-

cidence rate of the above outcomes was significantly elevated (Table); IRRs of ILD 31.8 [95% confidence interval:

13.2-76.7], cancer 2.36 [1.61-3.48], herpes zoster 1.75 [1.20-2.54], tuberculosis 2.08 [1.15-3.77], severely disabled sta-

tus 4.79 [2.55-9.01], and mortality 3.47 [1.96-6.12]. Among IIM patients, the presence of ILD or cancer greatly deterio-

rated survival; mortality IRR of 73.2 [9.58-559.9] in ILD and 63.2 [17.6-226.7] in cancer. The occurrence of zoster and

tuberculosis did not influence on the mortality. ILD and cancer also worsened functional impairment of IIM patients; IRR

of 12.0 [2.64-54.9] for severely disabled status in ILD and 13.2 [4.19-41.6] in cancer.

Conclusions: This is the first report of the nation-wide population based evaluation of IIM in Korea. The incidence of

ILD, cancers, zoster, and tuberculosis was exceptionally higher in IIM than non-IIM. ILD and cancers significantly af-

fected prognosis of IIM.

Table. Incidence rate and incidence rate ratios of major comorbidities, severely disabled, and death in patients with idiopathic inflammatory myositis versus the matched control

Incidence Rate (# of cases/1,000 person-year) Incidence Rate Ratio[95% Confidence interval]Myositis (n=91) Control (n=1820)

Interstitial lung disease 33.0 (13/394.3) 1.04 (8/7714.3) 31.8 [13.2-76.7]Cancer 73.6 (29/394.3) 31.1 (240/7714.3) 2.36 [1.61-3.48]Herpes zoster 76.1 (30/394.3) 43.6 (336/7714.3) 1.75 [1.20-2.54]Tuberculosis 30.4 (12/394.3) 14.6 (113/7714.3) 2.08 [1.15-3.77]Severely disabled 30.4 (12/394.3) 6.35 (49/7714.3) 4.79 [2.55-9.01]Death 35.5 (14/394.3) 10.2 (79/7714.3) 3.47 [1.96-6.12]

O-20-30


S100

C-Reactive Protein to Albumin as a New Prognostic Value and Clinical Significance in Patients with Dermatomyositis

Jaehyung Hur1, Dong Jin Go2, Sang Wan Chung1, You-Jung Ha1, Eun Ha Kang1, Jin Kyun Park2, Kichul Shin3, Eun Young Lee2, Eun Bong Lee2, Yeong Wook Song2,4, Yun Jong Lee1,2

1Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, 2Department of Internal Medicine, Seoul National University Hospital, Seoul, 3Division of Rheumatology,

Department of Internal Medicine, SMG-SNU Boramae Medical Center, Seoul, 4WCU Department of Molecular Medicine and Biopharmaceutical Sciences, Medical Research Institute, Seoul National University College of Medicine, Seoul, Korea

Background: Recent studies have suggested that C-reative protein to albumin (CRP/Alb) ratio could be an emerging

predictive marker of mortality in patients with sepsis or malignancies.

Objective: This study was aimed to evaluate the clinical significance and prognostic value of CRP/Alb ratio in patients

with dermatomyositis.

Methods: We retrospectively reviewed 158 patients with newly diagnosed dermatomyositis between August 2003 and

January 2016. We investigated the association of the CRP/Alb ratio with clinical characteristics. Using the receiver oper-

ating characteristics curves, the cut-off value of CRP/Alb ratio for predicting survival was calculated. Univariate and mul-

tivariate analyses using Cox proportional hazard model were performed to identify associated factors with survival.

Results: The optimal cut-off value of the CRP/Alb ratio was 0.073 for overall survival. According to the cut-off value

of 0.073, we classified 57 patients (36.1%) into the low CRP/Alb ratio group and 101 patients (63.9%) into the high

CRP/Alb ratio group. The higher CRP/Alb ratio group was associated with older age (≥50) (p=0.031), the lower per-

centage of DLco (p=0.006), overlap syndrome (p=0.018) and death (p=0.009). The CRP/Alb ratio was significantly cor-

related with muscle enzymes (creatine kinase: γ=0.248, p=0.002; lactate dehydrogenase γ=0.360, p<0.001; and aldo-

lase γ=0.170, p=0.048, respectively). In univariate analyses, high CRP/Alb ratio, old age, and the presence of inter-

stitial lung disease (ILD) were identified as significant factors for death. The higher CRP/Alb ratio and age >50 were

found to independently lower risk of survival by multivariate analysis (p=0.041 and p=0.006, respectively).

Conclusion: Our results demonstrated that higher level of the CRP/Alb ratio was associated with worse overall surviv-

al and the CRP/Alb ratio may play a role as an independent prognostic marker in patients with dermatomyositis.

O-20-31

(2010. 1. 1∼2010. 12. 31)


Breakfast Symposium


S103

Seeking for the Right ‘Combination’ of Conventional DMARDs in Rheumatoid Arthritis:

Options Beyond Triple Combination

Kichul Shin

Division of Rheumatology, SMG-SNU Boramae Medical Center

Early disease control in rheumatoid arthritis (RA) is not an optional, but an essential task for rheumatologists.

Especially, upfront combination of conventional disease modifying anti rheumatic drugs (cDMARDs) is recommended

in RA patients with poor prognosis. Preference of combination strategies vary among clinicians, and such regimens have

evolved since the introduction DMARDs. Triple therapy (methotrexate (MTX), hydroxychloroquine, sulfasalazine

(SSLZ)) or MTX plus SSLZ has been well studied, and is one of the mainstay regimens for combination therapy.

Alternatives, on the basis of MTX, have been published in the literature and are applied or often modified, in daily clinical

practice. Tacrolimus and leflunomide are relatively new agents used in combination with MTX. Results of both combina-

tion strategies respectively show reasonable efficacy and safety profiles in clinical studies. Now with a longer list of

cDMARDs at hand, the quest is to select the proper regimen for RA patients individually, understanding the known possi-

ble adverse events of each agent, and when it is combined with one another.

(2010. 1. 1∼2010. 12. 31)


류마티스학 연구재단 연구과제 결과 보고


S107

Impact of Patient Education on Outcomes in RA Patients

Yoon-Kyoung Sung, MD, PhD, MPH

Hanyang University Hospital for Rheumatic Diseases

Yoon-Kyoung Sung: Impact of Patient Education on Outcomes in RA Patients



S112

류마티스관절염환자 대상 교육용 앱개발과 환자교육중재가 약제순응도 및 치료결과에 미치는 효과

Seung In Baek, Ji Hoon Kim, Seung Min Jung, Ji Hyeon Ju, Sung-Hwan Park

가톨릭대학교 의과대학

Objective: This study was to measure alleviating effect of professional-led education on disease activity, and the param-

eters of assessment tools in rheumatoid arthritis (RA). Furthermore, we aimed to develop a cellular phone-based applica-

tion program which was specialized for educating patients with rheumatoid arthritis.

Methods: RA patients with disease activity of DAS28>3.2 were recruited in this research. Patients were randomly allo-

cated into two groups- one is education intervention group and the other is control group. Patients were systemically edu-

cated by the experienced professionals. The strategy of “Treat to target” was mainly used for educating patients. Patients

of education group were asked to fill up the forms showing target achievement at routine follow up periods. Disease activ-

ity, pain, dysfunction, fatigue, drug compliance, and quality of life were assessed at 0, 3 months, 6 months and 9 months

after study initiation. 2 sample t-test, Wilcoxon rank sum test, chi-square test or fisher’s exact test were used for stat-

istical analysis.

Results: Disease activity was more effectively controlled in education intervention group (DAS28 2.63 vs 3.34,

P=0.02). Visual analogue scale revealed at lower score (1.97 vs 4.06, P=0.02). Fatigue was improved in education group

by FACIT scale (42.39 vs 36.61, P=0.01). Illness perception score was better (22.5 vs 40.0, P<0.0001). Quality of life

shown by SF36 was also better (50.6 vs 47.1, P=0.01). However, Korean HAQ score and drug adherence score (MMAS-4)

was not significantly affected by educational intervention.

Conclusion: Subjective parameter such as fatigue and illness perception was improved by appropriate education led

by healthcare professional. Furthermore, purpose-driven education was objectively effective in controlling disease activ-

ity and improving quality of life. Patient education may need to vigorously be incorporated into the routine rheumatology

practice.

*For better educational support, smart phone-based application is under development. This content is temporarily

available by capturing QR code below or typing the internet address in smartphone internet window.


S113

질환특이 역분화 줄기세포 유도

정승민

연세대학교 의과대학 류마티스내과

역분화 줄기세포는 성체의 체세포를 이용하여 만들어진 전분화능을 갖는 세포로서, 배아줄기세포와는 달리 윤리적인 문제에서 비교

적 자유롭고, 중간엽 줄기세포보다 자가 복제 및 분화 능력이 뛰어나다는 장점을 갖고 있다. 특히 환자로부터 유래한 역분화 줄기세포는

질환과 유사한 환경을 조성하여 병인 연구에 이용되거나, 자가세포를 이용하여 이식의 거부반응을 최소화한 이식 재료로 활용될 수 있

다. 환자유래 역분화 줄기세포를 이용하는 연구에 있어서 중요한 점은 특징적인 환자군에서 수집한 검체를 이용하여 양질의 역분화 줄

기세포를 유도하고, 이로부터 신뢰성 있는 표적세포를 만드는 것이라고 할 수 있다. 역분화 줄기세포를 이용한 병인 연구는 주로 유전적

인 이상 소견을 갖는 환자에서 우선적으로 시도되었으나, 최근에는 유전적 소인을 갖는 만성 질환자에서도 질환 특성을 파악하는 데에

도움이 될 것으로 기대되고 있다. 환자의 역분화 줄기세포에서 유래한 표적세포는 정상인 또는 비교 질환군의 역분화 줄기세포에서 유

래한 세포와 형질 비교를 하게 되며, 그 차이는 일부 질환의 특성을 반영할 것으로 생각된다. 그러나 환자 개인의 특성에 의해서도 형질의

차이가 나타날 수 있으므로, 결과 해석에 유의를 요한다. 역분화 줄기세포를 이용한 재생 치료 연구에 있어서는, 무엇보다도 안전한 방법

으로 양직의 표적세포 또는 표적기관을 만들어내는 것이 중요하다고 할 수 있다. 또한 재생 치료를 위해 사용될 조직은 질환의 병태 생리

를 보이지 않으면서 조직의 특성상 낮은 면역원성을 갖는 것이 바람직하다. 최근 근골격계 질환 및 자가면역 질환에서도 역분화 줄기세

포를 이용한 연구가 점차 확대되고 있다. 성공적인 연구 수행을 위해서는, 환자에서 유래된 질환특이 역분화 줄기세포의 품질을 지속적

으로 관리하고, 역분화 줄기세포로부터 표적 세포로의 분화 효율을 높이면서 분화된 세포가 안정적인 형질을 갖도록 유지하는 것이 필

수적이라고 할 수 있을 것이다.


S114

Risk Factors of Herpes Zoster in Patients with Rheumatic Diseases in Korea

Hee Jung Ryu1, Jin-Ok Han2, Mi Ryoung Seo1, Hyo Jin Choi1, Kwang-Pil Ko2, Han Joo Baek1

1Department of Rheumatology Gachon University Gil Medical Center, 2Department of Preventive Medicine, Gachon University School of Medicine, Incheon, Korea

Background: Herpes zoster (HZ) is caused by the reactivation of latent varicella zoster virus infection and is associated

with a risk of disseminated infection and often considerable pain and morbidity. Older age and immunosuppressive medi-

cations are known as the established risk factors for HZ and other potential risk factors for HZ include ethnicity, generic

susceptibility, rheumatic diseases, trauma, and psychological stress. And the immunosuppressive medications and rheu-

matic diseases such as RA and SLE contribute to increase risk of HZ, however the comparative risk of HZ among different

immunosuppressive medications and different rheumatic diseases are unclear.

Objective: We performed this nationwide cohort study to determine the risk factors of HZ in patients with rheumatic

diseases in Korea.

Patients and Methods: We used the database of the Health Insurance Review & Assessment Service of Korea and ana-

lyzed the data of patients aged ≥18 years who had visited hospital more than two times with rheumatic diseases (RA,

SLE, Behçet’s disease, vasculitis, spondyloarthropathy, and other connective tissue diseases) as a principal diagnosis

from Jan 2009 to Oct 2013. HZ was identified as ICD-10 codes related to HZ with prescription of antiviral agents.

Demographic data, comorbidities (Hematologic malignancy, solid malignancy, diabetes, hypertension, heart diseases,

chronic lung diseases, chronic liver diseases, chronic renal diseases) and medications were analyzed as the risk factors

by using Cox proportional hazards models.

Results: The cumulative incidence of HZ in the patients with rheumatic diseases was 0.65%. The incidence rate (IR)

of period (per 10,000 person-years) was highest in RA (26.4) and followed the order in spondyloarthropathy (19.9), oth-

er connective tissue diseases (10.2), Behçet’s disease (6.2), SLE (5.1) and vasculitis (0.9). Compared with the reference

group of RA, HZ occurred more frequently in patients with SLE (hazard ratio [HR] 4.3, 95% CI 3.5-5.3) and Behçet’s dis-

ease (HR 4.5, 95% CI 3.7-5.6). And female, hematologic malignancy, hypertension, diabetes, chronic lung diseases, and

use of methotrexate, steroid, cyclosporine and TNF antagonists were independently associated with the development of

HZ. There was no apparent association of HZ with older age, spondyloarthropathy, and sulfasalazine in the patients with

rheumatic diseases.

Conclusion: Risk factors for HZ in patients with rheumatic diseases included SLE, Behçet’s disease, use of steroid and

immunosuppressive medications, and several comorbid medical conditions. Older age was not the independent risk fac-

tor in the patients with rheumatic diseases, unlike in general population.

(2010. 1. 1∼2010. 12. 31)


Special Lectures


S117

유도만능줄기세포의 연골세포 분화 및 Crispr/Cas9 유전자 가위 시스템의 확립

한승우

대구파티마 병원

골관절염은 대표적인 퇴행성 질환으로 연골세포의 비대화에 동반된 자멸사와 MMP13이나 ADAMTS 등의 효소에 의한 세포외기

질의 파괴가 핵심 병리 기전임. 그러나 이를 억제하여 골관절염을 예방하려는 시도는 골관절염의 느린 진행 경과로 인해 장기간의 치료

를 요하며, 골관절염으로 인해 증상이 발생하려면 관절연골의 손상이 일정 정도 이상 진행되어야 한다는 점에서 한계를 가짐. 이로 인해

손상된 연골을 중간엽 줄기세포나 자가 연골세포를 이용하여 복구하려는 시도들이 있어왔으나 대부분의 연구에서 만족스러운 결과를

얻지 못함. 연골세포는 증식능이 거의 없고, 일반적인 조건에서 배양할 경우 탈분화되어 연골세포의 성질을 잃게 됨. 일반적으로 손상된

연골의 수복을 위해서는 107개 이상의 많은 연골세포가 필요하나 이런 제한된 연골세포의 증식능으로 인해 치료에 충분한 연골세포를

얻기가 힘듬. 본 연구진은 혈관내피세포에 야마나카 인자를 도입하여 유도만능줄기세포로 분화 및 증식시키고, 이를 중간엽 세포 단계

를 거쳐 연골세포로 분화시키는 연구를 진행 중임. 이를 통해 충분한 수의 연골세포 확보가 가능하며, 골관절염의 치료에 적용하려고

함. 본 연구진이 진행 중인 두 번째 골관절염의 치료적 접근법은 Crispr/Cas9 유전자 가위 시스템을 이용하여 골관절염의 진행에 중요

한 타겟 단백을 결손시키는 방법임. 면역 반응이 없고, DNA에 삽입되지 않는 아데노연관 바이러스 시스템에 Crispr/Cas9 유전자 가위

시스템을 결합하여 관절연골에서 특정 단백을 결손하려함. 타겟 단백으로 제 2형 BMP 수용체나 Hif2a를 고려하고 있으며 동물실험을

통해 효과를 검증하려 함.


S118

T Cell Receptor Stimulation with Microbeads

김진현

충남대학교 의과대학

Triggering of the T cell receptor (TCR) by antigen presenting cells activates signaling networks. The signal trans-

duction will lead to transcriptional activation, proliferation, and differentiation of T cells that will ultimately result in an

immune response. Defects in signal cascades may lead to either T-cell hyper or hyporesponsiveness, which results in au-

toimmunity or immunodeficiency, respectively. Thus, the study of how TCR signaling is initiated, transduced, and con-

verted to a cellular response is important for the understanding physiology of T cells and the molecular mechanisms of

immunologic disease.

To assess signaling events during TCR activation, soluble stimuli such as agonistic antibodies against the TCR/CD3

complex and/or CD28 are still largely used. However, soluble stimuli fail to induce T-cell proliferation or appropriate

functional responses. Thus, it is questionable whether TCR signaling induced upon stimulation with soluble antibodies

reflects the physiologic signaling in T-cell responses. Alternative method of T-cell stimulation is based on microbeads

coated with the same antibodies against TCR complex and has been used mainly to expand T cells ex vivo. It is generally

believed that soluble antibodies and immobilized antibodies on microbeads have different functional properties.

However, a comprehensive biochemical characterization of antibody-coated microbeads stimulation in human T cells in

vitro has not yet been performed. Therefore, an analysis of the signaling signatures such as CD247, SLP76, Akt and

Erk1/2 was performed by antibodies against the TCR complex immobilized on microbeads.

The graded stimulation with anti-CD3- and anti-CD28-coated microbeads can provoke variable phosphorylation in

signaling molecules. The phosphorylation of proximal molecules like SLP76 and CD247 demonstrated positively corre-

lated response by graded TCR stimulation. However, the phosphorylation of distal molecules such as ERK1/2 and AKT

revealed initial increase with weak stimuli but steady state or even less phosphorylation with stronger TCR stimulation.

Between old and young persons, there was also a difference in the naïve T cell signal transduction. In old persons the

proximal signal molecule showed more phosphorylation than in young people whereas the distal molecule featured less

phosphorylation than in young persons.


S119

Change of Regulatory T Cells in RA Patients with Tocilizumab

Dam Kim

Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases

Background/Objectives: Various immune cells are considered to be involve in the pathogenesis of rheumatoid arthritis

(RA). The anti-interleukin (IL)-6 receptor antibody tocilizumab (TCZ), which is one of effective treatments against RA,

is supposed to affect proportions of peripheral blood cells by blocking the IL-6 signaling. We aimed to identify the effect

of TCZ treatment on proportion of peripheral blood cell population during 2 years of treatment.

Methods: Among RA patients who met the 1987 ACR classification of RA or the 2010 ACR/EULAR classification, con-

secutive patients at Keio University Hospital who commenced TCZ as their first biologic agent were enrolled. The pa-

tients were administered 8 mg/kg TCZ every 4 weeks, either with or without conventional DMARDs. Peripheral blood

mononuclear cells were obtained at baseline, at week 24, 52, and 104 of TCZ treatment. The proportion of several subsets

of peripheral cells with their levels of expression of differentiation markers, activation markers and costimulatory mole-

cules were measured sequentially from baseline to week 104 by flow cytometry analysis.

Results: Twenty two RA patients who completed 2 years of TCZ treatment were enrolled in this study. Among them,

17 patients achieved simple disease activity index (SDAI) remission at week 104 of TCZ therapy. The proportion of

CD4+CD25+CD127low Treg cells increased during week 52 and maintained from week 52 to week 104. Comparing pa-

tients with remission and non-remission at week 104, proportions of Treg cells were slightly higher in patients with re-

mission, but it was not statistically significant. In addition, proportion of HLA-DR+ Treg cells was increased during week

52 to 104.

Conclusion: TCZ affected proportions of circulating immune cells in patients with RA. The proportion of Treg cells

among CD4+ T cells increased with TCZ treatment.

(2010. 1. 1∼2010. 12. 31)


Invited Lectures II


S123

Engineering New Biologic Therapies for Osteoarthritis

Farshid Guilak, PhD

Center of Regenerative Medicine and Shriners Hospitals for Children - St. Louis, Departments of Orthopaedic Surgery, Developmental Biology, and Biomedical Engineering, Washington University, St. Louis MO

Osteoarthritis is a painful and debilitating disease of the joints that is characterized by progressive degeneration of the

articular cartilage that lines the joint surfaces. The etiology of osteoarthritis is poorly understood, although it is now well

accepted that biomechanical factors play an important role in the onset and progression of this disease. The primary goal

of our lab has been to determine the mechanisms by which mechanical loading affects the physiology of the joints. Using

a hierarchical approach to span different systems, ranging from clinical studies and in vivo animal models to studies at

the tissue, cellular, and subcellular scale, we have identified specific mechanical signaling pathways that regulate cartilage

physiology, pathology, and mechanically-induced regeneration. These pathways provide novel pharmacologic targets for

the modification of cartilage degeneration in osteoarthritis. Additionally, our studies have focused on tissue engineering

approaches for repairing cartilage damage with osteoarthritis. Using textile processes that allow weaving of biomaterial

fibers in three dimensions, we have created cell-instructive bioactive scaffolds that can recreate many of the complex bio-

mechanical properties and anatomic features of articular cartilage as a cell-based approach for complete resurfacing of os-

teoarthritic joint surfaces. In recent years, the advent of synthetic biology and gene-editing methods such as CRISPR/

Cas9 has allowed for precise modifying gene networks that control cell behavior. We have applied a combination of princi-

ples from these fields to rewire cellular gene circuits in a manner that allows us to create a unique, custom-designed cell

type that can sense and respond to its biochemical environment in a pre-programmed way to developed engineered tis-

sues with the ability for tunable, inducible, or feedback-controlled, auto-regulated biological responses. In addition to re-

capitulating the biochemical and biomechanical properties of the tissue, these “smart” constructs can provide controlled

drug delivery and immunomodulatory responses to the joint to enhance the success of engineered tissue replacements.

Taken together, these studies emphasize the important role of biomechanics and mechanobiology in the health, disease,

and regeneration of the joint.


S124

Pulmonary Arterial Hypertension in the Connective Tissue Diseases

Janet Pope, MD, MPH, FRCPC

Univ. of Western Ontario and St. Joseph's Health Care, London Ontario, Canada

Pulmonary arterial hypertension (PAH) can be a complication of connective tissue diseases (CTDs) where it is most

often occurring in systemic sclerosis (SSc). Routine screening in all CTDs is not recommended but it is recommended

in SSc and CTDs with SSc features such as those with overlaps including SSc and many with mixed connective tissue

disease. PAH must always be diagnosed with right heart catheterization. In CTDs, there are multiple reasons for dyspnea

so investigations have to be done as clinically indicated to determine if there is heart or lung involvement in someone with

shortness of breath and CTD.

PAH IN SYSTEMIC SCLEROSIS

Development of PAH in SSc is lethal with shorter survival than idiopathic PAH. It occurs in 8 to 15% of patients. Years

prior to diagnosis, there may be changes such as a decreasing diffusing capacity on pulmonary function testing and cardiac

exercise abnormalities, so screening of PAH in SSc is recommended. Research may aid in determining who has the great-

est chance of developing PAH. Those who are older with long standing disease, and a low, worsening diffusing capacity

seem to be at highest risk. When screening SSc patients (with annual echocardiography and/or pulmonary function tests

(diffusing capacity), patients are detected at earlier functional class and if treated early, they can have less worsening.

Therapies of PAH have reduced clinical worsening and improved mortality. Drugs used for PAH do result in sustained

clinical and hemodynamic improvements. Major classes of pharmacotherapeutics recommended for treatment of PAH in

SSc include: ERAs (macitentan bosentan, ambrisentan), PDE5 inhibitors (sildenafil, tadalafil), IV prostanoids

(epoprostenol, iloprost, treprostinil), and Riociguat (a soluble guanylate cyclase (sGC) stimulator). These drugs were

traditionally used as monotherapy; however, recent studies have shown benefit in combination therapy and further re-

search is ongoing in this respect. The standard of care for PAH is to add another treatment if initial treatment goals are

not reached with monotherapy and some expert centers initiate combination therapy as first-line. Trends have been to

treat PAH earlier with positive data from treatment of less symptomatic patients (Functional Class II).

In the class of ERAs, macitentan has improved relevant end points such as less hospitalizations and survival in PAH

where approximately 1/3 of patients had connective tissue disease (especially systemic sclerosis). ERA agents are also

being studied in combination therapies with PDE5 inhibitors. Sildenafil and tadalafil have shown clinical improvements

in patients with PAH as monotherapies.

Epoprostenol, an intravenous (IV) prostanoid, is considered the most effective. However, it is a synthetic compound

with a half-life of 5 minutes; thus, requiring an indwelling catheter and continuous infusion. Iloprost has been studied

in inhalation formulations in the setting of PAH. Current treatment recommendations include both inhalational and IV

forms. Treprostinil has been studied in IV, subcutaneous, inhalational and oral routes of administration in PAH, and is

Janet Pope: Pulmonary Arterial Hypertension in the Connective Tissue Diseases


usually given by chronic subcutaneous administration.

Riociguat is a soluble guanylate cyclase (sGC) stimulator, which is responsible for synthesis of cGMP that acts on the

cGMP-dependent protein kinase pathway, ultimately leading to vasodilation with improvement in the 6 minute walk test,

functional class, pulmonary vascular resistance and time to clinical worsening.

Data are lacking with respect to what order and which combination to use in each SSc patient with PAH. There is no

high level data in SSc with respect to the use of anticoagulation in PAH, although primary PAH (i.e. not associated with

SSc) treatment recommendations have suggested warfarin may be beneficial. Future trends include screening for PAH

early, determining if SSc patients who do not have symptoms should be treated if they have proven PAH and under-

standing the natural history of those who do not meet criteria for PAH but have abnormal pulmonary artery pressure and

normal wedge pressure (sometimes called borderline PAH). There are no definitive data that immune suppression in SSc

will treat PAH.

PAH IN SLE

PAH in SLE is treated similarly to SSc but also immune suppression is added. Always other causes of PH must be ruled

out. Patients with SLE are at higher risk than the general population of pulmonary emboli if they have antiphospholipid

antibodies. Patients need to have a ventilation perfusion lung scan and possibly a spiral CT chest looking for thrombi. The

prognosis of PAH in SLE is better than SSc.

CONCLUSIONS

PAH should be suspected in someone with CTD and unexplained dyspnea. A systematic approach is needed and in SSc

or SSc-like CTDs, screening for PAH is needed due to the high prevalence and because screening allows for earlier inter-

vention and a better prognosis.

SELECTED REFERENCES

1. Murdaca G, Spano F, Puppo F. Current therapies for the treatment of systemic sclerosis-related pulmonary arterial hypertension: efficacy and safety. Expert Opin Drug Saf. 2014 Mar;13(3):295-305.

2. Muangchan C, Baron M, Pope J. The 15% rule in scleroderma: the frequency of severe organ complications in systemic sclerosis. A systematic review. J Rheumatol. 2013 Sep;40(9):1545-1556.

3. Pulido T, Adzerikho I, Channick R, et al. Macitentan and morbidity and mortality in pulmonary arterial hypertension. N Engl J Med. 2013;369(9):809-818.

4. Ghofrani HA, Galie N, Grimminger F, Grunig E, Humbert M, Jing ZC, et al. Riociguat for the treatment of pulmonary arterial hypertension. N Engl J Med. 2013 Jul 25;369(4):330-340.

5. Rubin LJ, Galie N, Grimminger F, Grunig E, Humbert M, Jing ZC, et al. Riociguat for the treatment of pulmonary arterial hyper-tension: a long-term extension study (PATENT-2). Eur Respir J. 2015 May;45(5):1303-1313.

6. Olsson KM, Delcroix M, Ghofrani HA, Tiede H, Huscher D, Speich R, et al. Anticoagulation and survival in pulmonary arterial hy-pertension: results from the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA). Circulation. 2014 Jan 7;129(1):57-65.


S126

Ultrasound in Rheumatology: Getting Closer to the Holy Grail?

GAW Bruyn, MD, PhD

Department of Rheumatology, MC Groep Hospitals, Lelystad, The Netherlands

By 2016, musculoskeletal ultrasound (US) can no longer be considered as controversial in rheumatology but on the

contrary, thrives as an established imaging modality for the investigation and management of chronic inflammatory

arthritis. The main advantage of US in the evaluation and monitoring of patients with rheumatoid arthritis (RA) is based

particularly on its greater sensitivity compared to clinical examination for detecting synovitis in RA signature joints. Yet,

the development of US as a tool for the clinical rheumatologist has come a long way. The several milestones set in stand-

ardizing the use of US in rheumatic disease over the last decade and the contribution of US in understanding muscu-

loskeletal diseases will be presented in this lecture, that will focus on RA.

More or less arbitrarily, we may state that the start of a data-driven development of US as a research instrument was

designed in 2004. At the OMERACT conference of 2004, a Special Interest Group (SIG) dedicated to ultrasound was

founded by a group of international rheumatologists/experts in ultrasound, with the aim of exploring the metric proper-

ties of musculoskeletal US. At this infant stage, a systematic review of the musculoskeletal US literature in rheumatoid

arthritis (RA) had dissected the various gaps in existing knowledge, particularly underscoring the lack of US definitions

of rheumatic pathology, instrument reliability, and instrument validity. Unfortunately, research resources of the SIG were

very limited and so, efforts had to be strictly prioritized. The very first publication of the group reported on a core set of

practical US definitions for inflammatory elementary lesions including synovitis, tenosynovitis, and erosions. In consid-

ering which best strategy to employ, dauntless exercises on synovitis in RA patients were carried out during the

2004-2010 era. Standardization of detection and acquisition of synovitis in metacarpophalangeal (MCP) joints in RA us-

ing the OMERACT definition for synovitis, i.e. a combination of effusion and synovital hypertrophy, was considered the

first objective. Subsequent iterative exercises tested and retested interobserver and intraobserver reliability for both the

reading and acquisition of images of the MCP joint, including a freshly introduced semi-quantitative scoring system at

the joint level that combined together power Doppler (PD), effusion and synovial hypertrophy. The B-mode semi-

qauntitative scoring system included 4 steps (grades 0-3), the PD scoring system also included 4 grades (0-3). These data

showed that the OMERACT ultrasound definitions and scoring system of synovitis combined with a standardized acquis-

ition protocol provided good intra- and interobserver reliability.

Subsequently, the definitions and scoring system of synovitis were evaluated on other joints commonly involved in RA,

including proximal interphalangeal joints (PIPJ), wrist, metatarsophalangeal joints (MTPJ), and knee joints. Two should-

er reliability studies were also conducted to compare ultrasound with magnetic resonance imaging for the detection of

inflammatory and mechanical pathologies and to assess the intra- and inter-observer reliability of ultrasound for detect-

ing these lesions. All data were published in peer-reviewed journals, and showed that the developed PDUS scoring of

MCP synovitis was useful for detection and scoring of synovitis in other joints.

In the last phase, the objectives changed from joint level to patient level. This project was called the OMERACT ultra-

GAW Bruyn: Ultrasound in Rheumatology: Getting closer to the Holy Grail?


sound global synovitis score at the patient level (US-GLOSS) using the combined PDUS score in an extended set of joints.

The ultimate goal of an ultrasound scoring system at patient level is permitting physicians objectively follow patients un-

der treatment in clinical practice and research by using a feasible and economical tool which we would expect to be more

representative of RA disease activity than conventional clinical measures. The US-GLOSS has been used in various clin-

ical trials, but fails to show a consistent correlation with several clinical and functional instruments. At this moment, it

is still unclear how many joints we have to scan in order to get a validated reflection of the disease activity, neither is there

consensus on the scanning technique of the various joints. These issues are still under investigation.

In conclusion, collaborative work over the years, by an international group of rheumatologists/US experts has yielded

considerable progress in developing a valuable instrument that can be used in a both in daily clinical practice and in rheu-

matology trials.

(2010. 1. 1∼2010. 12. 31)



Basic Aspects


S131

Regulation of Autophagic Flux Alters Interleukin-17A-induced Migration and Proliferation of Fibroblast-like Synoviocytes

from the Patients with Rheumatoid Arthritis

Ji-Min Kim1, Jihye Bang2, Hye-Jin Jeong1, Chang-Nam Son1, Sang-Hyon Kim1

1Division of Rheumatology, Department of Internal Medicine, Keimyung University School of Medicine, Dongsan Medical Center, Daegu, 2Keimyung University Graduate School of Medicine, Daegu, Korea

Background: Interleukin-17A (IL-17A) plays a critical role in the pathogenesis of rheumatoid arthritis (RA).

Autophagy is required to ensure cellular homeostasis. Here, we hypothesized that IL-17A might have an impact on auto-

phagic flux and that aberrant autophagy might be involved in expansion of synovial fibroblasts in the patients with RA.

Objectives: The aims of this study were (1) to evaluate whether IL-17A influences on autophagic flux in the synovium

of the patients with RA and (2) to investigate whether the modulation of autophagy can regulate migration and pro-

liferation of fibroblast-like synoviocytes (FLS) from the patients with RA (RA-FLS) under inflammatory milieu.

Methods: Synovial tissue was obtained from the patients with RA or osteoarthritis (OA). FLS was cultured with

IL-17A, autophagy inducer or inhibitor. The expression of marker proteins for autophagic flux and the formation of auto-

phagolysosome were analyzed by western blot. A migration scratch assay was used to assess FLS migration in response

to stimulation with IL-17A. Proliferation of FLS was determined by the viable cell count using trypan blue. Bafilomycin

was used for inhibiting autophagic flux.

Results: The expression of autophagy markers (LC3B, Beclin1, Atg5) was increased in the synovium of the patients

with RA than in that of the patients with OA. Autophagy was also enhanced in RA-FLS compared with OA-FLS. IL-17A

upregulated the expression of LC3B, Atg5, Beclin1, LAMP1 in RA-FLS. In particular, IL-17A-induced accumulation of

p62 was prominent in RA-FLS. Migration and proliferation of FLS stimulated by IL-17A was suppressed by the inhibition

of autophagy.

Conclusion: This study reveals that IL-17A stimulates autophagic flux and that intervention of autophagy can control

IL-17A-induced migration and proliferation of FLS. Our results also provide additional evidence for a significant role of

autophagy in the pathogenesis of RA.

O-21-01


S132

Interleukin-32 Exacerbates Synovial Inflammation and Bone Destruction Via the Suppression

of Raf Kinase Inhibitory Protein

Hae Sook Noh1, Hye Song Lim1, Sang Mi Yi1, Min-Gyu Jeon1, Beow Yong Park2, Hee Young Cho2, Young-Sool Hah2, Yun-Hong Cheon1, Sang-Il Lee1

1Department of Internal Medicine and Institute of Health Science, Gyeongsang National University School of Medicine, Jinju, Gyeongnam, 2Clinical Research Institute, Gyeongsang National University Hospital, Jinju, Gyeongnam, Korea

Background: IL-32 is a newly described pro-inflammatory cytokine and play pathogenetic role in RA by stimulating

TNF-a production and activation of NF-kB and ERK pathways. Raf kinase inhibitory protein (RKIP) has been reported

to be an inhibitory protein for the NF-kB and ERK pathways. However, there was no study about the interaction of IL-32

and RKIP in RA.

Objective: The purpose of present study was to investigate the interaction of IL-32 and RKIP in RA.

Methods: Arthritis development was examined in IL-32 transgenic (TG) and wild-type of C57/BL6 (WT) mice using

the K/BxN serum transfer arthritic model. Fibroblast-like synoviocytes (FLS) and bone marrow-derived osteoclast were

isolated and cultured from IL-32 TG and WT mice. Synovium and FLS from RA patients were also used. Quantitive

RT-PCR, immunohistochemistry, ELISA, western blotting, TRAP and safranin-O staining, migration and invasion assay

were performed.

Reasults: IL-32 TG mice displayed significantly increased arthritis severity as assed by measurements of ankle swel-

ling, joint inflammation, and bone and cartilage erosions in the K/BxN serum-transfer model. TNF-a levels were sig-

nificantly increased in the serum and ankle of IL-32 TG mice than WT. RKIP expressions were decreased in the ankles,

FLS, and bone marrow-derived osteoclast of the IL-32 TG mice than WT. Additionally, RKIP expression was also de-

creased in the synovium and FLS from RA patients than osteoarthritis. The migration of FLS and osteoclastogenesis of

bone marrow-derived osteoclast of the IL-32 TG mice were increased than WT.

Conclusion: These results suggest pro-inflammatory role of IL-32 is, in part, RKIP-dependent. Thus, further studies

on the potential involvement of IL-32-RKIP axis will be beneficial in better understanding the pathogenesis of RA.

Keyword: IL-32, RKIP, Rheumatoid arthritis, Fibroblast-like synoviocytes, Osteoclastogenesis

O-21-02


S133

NFAT5 Promotes Macrophage Survival by Inducing Chemokine Ligand 2

Susanna Choi1, Sungyong Yoo2, Soo Youn Choi3, H. Moo Kwon3, Hyun-Sook Kim4, Daehee Hwang5, Chul-Soo Cho1,6, Wan-Uk Kim1,6

1POSTECH-Catholic BioMedical Engineering Institute, The Catholic University of Korea, Seoul, Korea, 2Department of Surgery and Biomedical Sciences, Cancer Biology Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA,

USA, 3School of Nano-Bioscience and Chemical Engineering, Ulsan National Institute of Science and Technology, Ulsan, 4Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, 5Center for Systems Biology of Plant Senescence

and Life History, Institute for Basic Science, Daegu Gyeongbuk Institute of Science and Technology, Daegu, 6Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea

Apoptotic death of activated macrophages is important for controlling chronic inflammation and its defect in these

cells has been implicated in the pathogenesis of rheumatoid arthritis (RA). However, the molecular signatures defining

apoptotic resistance of RA macrophages have not been fully understood. Here, global transcriptome profiling of RA mac-

rophages revealed that nuclear factor of activated T-cells 5 (NFAT5), an osmoprotective transcription factor, is one of the

critical regulators for a wide range of pathologic processes of synovial macrophages, including cell cycle, apoptosis, and

proliferation. Analysis of transcriptomes in NFAT5-deficient macrophages demonstrated the molecular networks defin-

ing cell survival and proliferation. Proinflammatory M1 polarizing stimuli and hypoxic conditions were responsible for

enhanced NFAT5 expression in RA macrophages. An in vitro functional study demonstrated that NFAT5-deficient mac-

rophages were more susceptible to apoptotic death. Interestingly, chemokine (C-C motif) ligand 2 (CCL2) was secreted

in an NFAT5-dependent fashion and it bestowed RA macrophages apoptotic resistance. Mice with NFAT5 hap-

loinsufficiency (NFAT5+/-) had a lower severity of IL-1β-induced arthritis than their wild type littermates. Moreover,

in mice, NFAT5-deficient macrophages were more susceptible to apoptosis and were less efficient in promoting joint de-

struction than NFAT5-sufficient macrophages when injected intra-articularly. Conclusively, NFAT5 regulates macro-

phage survival by inducing CCL2 secretion. Our results provide the first evidence that NFAT5 expression in macrophages

enhances chronic arthritis by conferring apoptotic resistance to activated macrophages and thereby plays a central role

in the pathogenesis of macrophage-dependent chronic inflammatory diseases, including RA.

O-21-03


S134

Autophagy Contributes to Celecoxib-induced Cell Death in Rheumatoid Arthritis Fibroblast-like Synoviocytes

Jihye Bang1, Hye-Jin Jeong2, Chang-Nam Son2, Ji-Min Kim2, Sang-Hyon Kim2*1Keimyung University Graduate School of Medicine, Daegu, 2Division of Rheumatology, Department of Internal Medicine,

Keimyung University School of Medicine, Dongsan Medical Center, Daegu, Korea

Background: An aggressive proliferation of synovium is the hallmark of rheumatoid arthritis (RA). Previous studies

suggested that resistance of fibroblast-like synoviocytes (FLS) to apoptosis is involved in synovial hyperplasia in the pa-

tients with RA. Recently, the possibilities that autophagy regulates apoptosis resistance and hyperplasia of FLS were also

presented. Selective cyclooxygenase-2 (COX-2) inhibitor, celecoxib, has been reported to affect apoptosis or autophagy

in various cancer cells.

Objectives: The aim of this study is to investigate the influence of celecoxib on viability of RAFLS and to reveal how

celecoxib affects the viability of RAFLS.

Methods: RA synovial tissue was obtained from patients during total knee replacement surgery or arthroscopy. FLS

was cultured with celecoxib, caspase inhibitor (z-VAD-fmk) or autophagy inhibitor (3-methyladenine; 3-MA, bafilomy-

cin A1; bafi A1, chloquine; CQ). Cell viability was measured by MTS assay and by cell count using trypan blue staining.

The expression of autophagy flux (LC3, p62) and apoptosis related protein (caspase3 and poly (ADP-ribose) polymerases

(PARP)) was analyzed by western blot.

Results: Celecoxib dose-dependently decreased cell viability (mean IC50 of 120μM) of RAFLS. Activation of Caspase

3 and PARP cleavage were observed in RAFLS after the treatment with celecoxib. Combination treatment with caspase

inhibitor and celecoxib increased cell viability than a single treatment with celecoxib. Celecoxib also increased the ex-

pression of LC3II and p62 in RAFLS. Treatment with autophagy inhibitor (3-MA, bafi A1, CQ) restored viability of RAFLS

which was decreased by celecoxib.

Conclusion: This study demonstrates that both apoptosis and autophagy contribute to celecoxib-induced cell death in

RAFLS. Further studies to identify the effects of celecoxib on chronological sequence of autophagy and apoptosis in

RAFLS are need.

O-21-04


S135

Robust Therapeutic Efficacy of Matrix Metalloproteinase-2 Cleavable fas-1-RGD Peptide

Complex on Chronic Inflammatory Arthritis

Eon Jeong Nam*, Jin Hee Kang, Keum Hee Sa, Shijin Sung, Jeong Soo Eun, Na Ri Kim, Young Mo Kang

Department of Internal Medicine, Kyungpook National University School of Medicine, (Rheumatology) Daegu, Korea

Background: Therapeutic agents that are transformable via introducing cleavable linkage by locally enriched MMP-2

within inflamed synovium would enhance therapeutic efficacy on chronic inflammatory arthritis. Transforming growth

factor-β-inducible gene-h3 (βig-h3), which consists of fas-1 domains and an Arg-Gly-Asp (RGD) motif, intensifies in-

flammatory processes by facilitating adhesion and migration of fibroblast-like synoviocyte in the pathogenesis of rheu-

matoid arthritis (RA).

Objectives: To investigate whether MMP-2 cleavable peptide complex consisted of fas-1 domain and RGD peptide

blocks the interaction between βig-h3 and resident cells and leads to the amelioration of inflammatory arthritis.

Methods: We designed βig-h3-derivatives, including the fourth fas-1 domain truncated for H1 and H2 sequences of

mouse (MFK00) and MMP-2-cleavable peptide complex (MFK902). MMP-2 selectivity was examined by treatment with

a series of proteases. MFK902 efficacy was determined by the adhesion and migration assay with NIH3T3 cells in vitro

and collagen-induced arthritis (CIA) model in vivo.

Results: MFK902 was specifically cleaved by active MMP-2 in a concentration-dependent manner, and βig-h3-me-

diated adhesion and migration were more effectively inhibited by MFK902, compared with RGD or MFK00 peptides. The

arthritis activity of murine CIA, measured by clinical arthritis index and incidence of arthritic paws, was significantly

ameliorated after treatment with all dosages of MFK902 (1, 10, and 30 mg/kg). MFK902 ameliorated histopathologic de-

terioration and reduced the expression of inflammatory mediators simultaneously with improvement of clinical features.

Conclusions: The present study reveals that the MMP-2-cleavable peptide complex, based on βig-h3 structure, was

a potent therapeutic agent for chronic inflammatory arthritis and provides a reliable evidence for the MMP-2-cleavable

mechanism as a tissue-targeted strategy to treat RA.

O-21-05

(2010. 1. 1∼2010. 12. 31)



Clinical Aspects II


S139

Disease Characteristics and Change of Arthritis Activity According to Treatment in Hepatitis B Surface Antigen

Positive Rheumatoid Arthritis Patients

YeongHee Eun, In Young Kim, Hyemin Jeong, Hyungjin Kim, Jaejoon Lee, Eun-Mi Koh, Hoon-Suk Cha

Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine

Background: Rheumatoid arthritis (RA) treatment may differ according to hepatitis B state and consequently bring

about different outcome of arthritis. However, it has not yet been elucidated whether hepatitis B affects treatment out-

come such as disease activity.

Objective: We investigated possible differences in change of arthritis activity between RA patients according to con-

comitant hepatitis B virus infection.

Methods: A retrospective analysis of 40 hepatitis B surface antigen (HBsAg)-positive RA patients and 112 HBsAg-neg-

ative RA patients was conducted. The longitudinal relationship between HBsAg-positivity and RA activity/medication

use was analyzed using generalized estimating equations in regression models.

Results: In regression analysis, RA activity showed time-dependent improvement. We observed significant interaction

between time and HBsAg-positivity for disease activity score in 28 joints with 3 variables (DAS28-3; P=0.026), that

means the degree of decrease in DAS28-3 with time influenced by HBsAg-positivity. But this interaction did not remain

significant after adjustment. For tender joints, erythrocyte sedimentation rate and C-reactive protein levels, there were

no interaction between time and HBsAg-positivity, while swollen joints showed significant interaction (P=0.017). The

time-association and group differences were not observed in alanine aminotransferase (ALT) level. Over all visits,

HBsAg-positive patients were less likely to receive methotrexate (OR 0.09 [95% CI 0.04-0.19], P<0.0001) and more like-

ly to receive sulfasalazine (OR 3.67 [95% CI 1.94-6.95], P<0.0001).

Conclusion: There were no significant differences over time in DAS28-3, tender joints and inflammatory markers ac-

cording to HBsAg-positivity, while swollen joints showed significant difference over time. ALT level did not showed

time-association and group differences. HBsAg-positive RA patients were less likely to receive methotrexate and more

likely to receive sulfasalazine.

O-21-06


S140

Correlations between Rheumatoid Arthritis Activity Indices and Factors Affecting Acute Phase Reactants

in Patients with Rheumatoid Arthritis

In Ah Choi

Division of Rheumatology, Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Korea

Background: Assessment of disease activity is a key part of clinical decision in rheumatology care.

Objectives: We compared the DAS28ESR and DAS28CRP to other RA activity measures and were to find confounding

factors affecting acute phase reactants to patients with RA to find best tool to access RA disease activity.

Methods: A cross-sectional study was conducted in 1120 patients with RA, using initial registration data from Korean

Biologics Registry (KOBIO).

Results: DAS28CRP showed excellent correlation with SDAI (r=0.926, p<0.001) and CDAI (r=0.901 p<0.001).

DAS28ESR also showed good correlation with SDAI (r=0.875, p<0.001) and CDAI (r=0.886, p<0.001). CRP showed

low but significant correlation with SJC (r=0.132, p<0.001), TJC (r=0.087, p=0.004), SDAI (r=0.441, p<0.001) and

CDAI (r=0.134, p<0.001). ESR also showed significant correlation with SJC (r=0.132, p<0.001), TJC (r=0.063,

p=0.035), SDAI (r=0.233, p<0.001) and CDAI (r=0.145, p<0.001). In correlation analysis using CDAI as controlled

variable, ESR increased with age (r=0.110, p<0.001) and serum RF (r=0.105, p=0.001) but was not correlated with

BMI, disease duration, and anti-CCP antibody titer. There was no difference in ESR according to the gender, smoking sta-

tus, presence of diabetes mellitus, obesity (BMI ≥ 30) or low body weight (BMI<18.5). In the same analysis, CRP was

not correlated with age, BMI, disease duration, RF and anti-CCP antibody. It was higher in male compared to female

(p=0.001) and higher in ever-smoker compared to never-smoker (p=0.027). There was no difference in CRP according

to the presence of diabetes mellitus, obesity or low body weight.

Conclusion: Both DAS28CRP and DAS28ESR were well correlated with other activity indices. ESR increased with age

but was less susceptible to gender or smoking status compared to CRP, suggesting DAS28ESR to be a more useful marker

for inter-patient-comparison of RA disease activity.

O-21-07


S141

Achievement of Imaging Remission among Patients with Rheumatoid Arthritis in Clinical Remission and

Their Characteristics

Ji-Young Choi, Seung-Jae Hong, Hyung-In Yang, Sang-Hoon Lee, Ran Song, Yeon-Ah Lee

Division of Rheumatology, Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Korea

Background & Object: Therapeutic goal of rheumatoid arthritis (RA) is to achieve disease remission. However, several

remission criteria have not always equated to the complete absence of true inflammation. Power Doppler

Ultrasonography (PDUS) has been demonstrated to detect subclinical synovitis. The aim of this study was to elucidate

the achievement rates of imaging remission and examine characteristics associated with achievement status among RA

patients in clinical remission.

Methods: This study was conducted in 46 RA patients who attained clinical remission, defined by DAS28-ESR re-

mission criteria. PDUS was performed in 16 joints and 2 tendons and graded on the basis of a dichotomous assessment

(presence/absence). Imaging remission was defined by absence of PD on US examination. The clinical and laboratory da-

ta of patients with imaging remission were compared with those of patients with only clinical remission.

Results: Twenty one patients (45.7%) with RA in clinical remission had PDUS-defined active synovitis. PD was de-

tected most frequently in right RC joint (n=12, 26.1%). Six patients complained of pain in other joints that were not in-

cluded in US assessments. All those joint were PDUS positive. PDUS negative patients had lower evaluator global assess-

ment score (P<0.001), and simplified disease activity index score, SDAI (P=0.005). They use less nonsteroidal anti-in-

flammatory drug (NSAID) (n=15 vs 19 pa-

tients, p=0.019). Overall, imaging remission

was related with less tender and swollen joint

count, lower patient global assessment score,

higher health assessment questionnaire (HAQ)

score and lower clinical disease activity score.

Conclusion: Achievement rate of imaging

remission was 54.3% in RA patients with clin-

ical remission. Patients who were in imaging

remission tend to have lower disease activity,

lower pain score and less frequent use of

NSAIDs, compared to patients with only clin-

ical remission.

O-21-08


S142

HAQ Score is an Independent Predictor of Sustained Remission in Patients with Rheumatoid Arthritis

Kyung-Eun Lee, Ji-Hyoun Kang, Yi-Rang Yim, Ji-Eun Kim, Jeong-Won Lee, Lihui Wen, Dong-Jin Park, Tae-Jong Kim, Yong-Wook Park, Shin-Seok Lee

Department of Rheumatology, Chonnam National University Medical School & Hospital, Gwangju, Korea

Objective: We compared remission rates, according to different definitions of remission in rheumatoid arthritis (RA)

and investigated the potential predictors of sustained remission at the 2-year follow-up.

Methods: We obtained data on 291 RA outpatients, seen from July 2009 to September 2012. Sociodemographic data

and answers to questionnaires were collected in face-to-face interviews. Remission was defined according to the Disease

Activity Score in 28 joints (DAS28)-ESR, DAS28-CRP, Simplified Disease Activity Index (SDAI), Clinical Disease Activity

Index (CDAI), and ACR/EULAR Boolean definition. Sustained remission was defined as when the patient continued in

remission at two consecutive annual assessments. Predictors of sustained remission according to the DAS28-CRP were

assessed by univariate and multivariate analyses.

Results: For the 291 RA patients, the remission rates of RA were 17.9% (DAS28-ESR), 54.3% (DAS28-CRP), 10.3%

(SDAI), 10.0% (CDAI), and 5.8% (Boolean). On follow-up for 2 years, the sustained remission rates of RA were 46.5%

(DAS28), 55.0% (DAS28-CRP), 37.5% (SDAI), 32.0% (CDAI), and 30.8% (Boolean). RA patients who achieve sus-

tained remission according to the DAS28-CRP were younger, and had more education, higher monthly income, lower

Health Assessment Questionnaire (HAQ) score, lower physician global assessment, lower patient global assessment,

lower patient pain assessment, and higher EQ-5D. In multivariate analysis, only the HAQ score predicted sustained re-

mission according to DAS28-CRP (OR=0.257, 95% CI 0.067-0.980, p=0.047).

Conclusion: The remission rates of RA patients differed according to the definition of remission, and the highest sus-

tained remission rate was classified by the DAS28-CRP. A lower HAQ score was an independent predictor of sustained

remission over 2 years, according to the DAS28-CRP.

O-21-09

(2010. 1. 1∼2010. 12. 31)


Research Society Session on Spondyloarthritis

1부 - 강직성 척추염에서 TNF 길항제의 사용


S145

Drug Survival of Tumor Necrosis Factor α Inhibitors in Patients with Ankylosing Spondylitis in Korea

Hyemin Jeong1, Yeong Hee Eun1, In Young Kim1, Hyungjin Kim1, Joong Kyong Ahn2, Jaejoon Lee1, Eun-Mi Koh1, Hoon-Suk Cha1

1Department of Medicine, Samsung Medical Center, 2Kangbook Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea

Objectives: To evaluate drug survival of the tumor necrosis factor-α inhibitors (TNFi) and risk factors for the drug dis-

continuation in patients with ankylosing spondylitis (AS).

Methods: We retrospectively evaluated 487 AS patients at a single tertiary hospital. Among the TNFi users, drug sur-

vival and risk factors of TNFi discontinuation were investigated.

Results: Among 487 patients, 128 AS patients were treated with at least one TNFi. Patients who were treated with

TNFi were younger at disease onset, had more peripheral manifestations, and had higher level of acute phase reactants

and BMI than those of TNFi non-users at baseline. Of 128 patients, 28 (21.9%) patients discontinued first TNFi therapy

during the follow-up period of 65.1±27.9 months. In the multivariable analysis, female (HR 6.08, 95% CI 2.27-16.27,

p=0.003), hip involvement (HR 2.52, 95%CI 1.08-5.87, p=0.033) and a high CRP (HR 1.10, 95%CI 1.00-1.21, p=0.044)

were risk factors for drug discontinuation. Etanercept showed better survival rate than infliximab. The main reason for

discontinuation of TNFi was inefficacy.

Conclusions: TNFi discontinuation rate of Korean patients with AS seems to be similar to those with the European

patients. Female sex, hip involvement, CRP, and the type of TNFi were associated with TNFi discontinuation.


S146

Safety of Resuming Tumor Necrosis Factor Inhibitors in Ankylosing Spondylitis Patients Concomitant with the

Treatment of Active Tuberculosis: A Retrospective Nationwide Registry of the Korean Society of Spondyloarthritis Research

Hye Won Kim1, Seong Ryul Kwon2, Kyong-Hee Jung2, Seong-Kyu Kim3, Han Joo Baek4, Mi Ryung Seo4, So-Young Bang5, Hye-Soon Lee5, Chang-Hee Suh6, Ju Yang Jung6, Chang-Nam Son7, Seung Cheol Shim8,

Sang-Hoon Lee9, Seung-Geun Lee10, Yeon-Ah Lee11, Eun Young Lee12, Tae-Hwan Kim13*, Yong-Gil Kim14*, and for the members of Korean Society of Spondyloarthritis Research

1Department of Internal Medicine, Yonsei University College of Medicine. Division of Rheumatology, Gangnam Severance Hospital, Seoul, 2Division of Rheumatology, Department of Internal Medicine, Inha University School of Medicine, Incheon, 3Division of Rheumatology, Department of Internal Medicine, Arthritis and Autoimmunity Research Center, Catholic University of Daegu School of Medicine, Daegu,

4Division of Rheumatology, Department of Internal Medicine, Gachon University Gil Hospital, Incheon, 5Division of Rheumatology, Department of Internal Medicine, Hanyang University Guri Hospital, Guri, 6Division of Rheumatology, Department of Internal Medicine, Ajou

University Hospital, Suwon, 7Division of Rheumatology, Department of Internal Medicine, Keimyung University Dongsan Medical Center, Daegu, 8Division of Rheumatology, Department of Internal Medicine, Chungnam National University Hospital, Daejeon, 9Department of

Rheumatology, Center of Arthritis and Rheumatism, Kyung Hee University Hospital at Gangdong, Seoul, 10Division of Rheumatology, Department of Internal Medicine, Pusan National University Hospital, Busan, 11Division of Rheumatology, Department of Internal Medicine,

Kyung Hee University Medical center, Seoul, 12Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Seoul, 13Division of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, 14Division of Rheumatology,

Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea

Backgrounds: Patients who develop an active tuberculosis infection during tumor necrosis factor (TNF) inhibitor

treatment typically discontinue TNF inhibitor and receive standard anti-tuberculosis treatment. However, there is cur-

rently insufficient information on patient outcomes following resumption of TNF inhibitor treatment during ongoing an-

ti- tuberculosis treatment. Our study designed to investigate the safety of resuming TNF inhibitors in ankylosing spondy-

litis (AS) patients who developed tuberculosis as a complication of the use of TNF inhibitors.

Methods: Through the nationwide registry of the Korean Society of Spondyloarthritis Research, 3929 AS patients who

were prescribed TNF inhibitors were recruited between June 2003 and June 2014 at fourteen referral hospitals. Clinical

information was analyzed about the patients who experienced tuberculosis after exposure to TNF inhibitors. The clinical

features of resumers and non-resumers of TNF inhibitors were compared and the outcomes of tuberculosis were sur-

veyed individually.

Findings: Fifty-six AS patients were treated for tuberculosis associated with TNF inhibitors. Among them, 23 patients

resumed TNF inhibitors and these patients were found to be exposed to TNF inhibitors for a longer period of time and

experienced more frequent disease flare up after discontinuation of TNF inhibitors compared with those who did not

resume. Fifteen patients resumed TNF inhibitors during anti-tuberculosis treatment (early resumers) and 8 after com-

pletion of anti-tuberculosis treatment (late resumers). Median time to resuming TNF inhibitor from tuberculosis was 3.3

and 9.0 months in the early and late resumers, respectively. Tuberculosis was treated successfully in all resumers and did

not relapse in any of them during follow-up (median 33.8 (IQR; 20.8-66.7) months).

Conclusions: Instances of tuberculosis were treated successfully in our AS patients, even when given concomitantly

with TNF inhibitors. We suggest that early resuming TNF inhibitors in AS patients could be safe under effective coverage

of the tuberculosis.


S147

Low Dose Etanercept Treatment for Maintenance of Clinical Remission in Ankylosing Spondylitis

박준원

서울대학교 의과대학

Objective: To investigate the efficacy and safety of low-dose etanercept treatment after clinical remission of ankylosing

spondylitis (AS) in the real world.

Methods: Data on 134 AS patients who were treated with etanercept for more than 12 months and achieved clinical

remission (BASDAI<4 and CRP<0.5 mg/dL) were extracted from a large single center registry. Drug survival and in-

cidence of adverse events in 100 patients who reduced the dose during follow up (low-dose group) were compared with

34 patients who maintained the initial dose (standard-dose group). For minimization of selection bias between the two

groups, the same analyses were performed in a propensity score-matched population.

Results: Both groups showed similar BASDAI score and CRP levels during the follow-up. Drug survivals between the

two groups were also comparable up to 4 years (vs. standard-dose group, adjusted HR=0.472, 95% CI 0.155-1.435). The

same analysis performed after propensity score-matching showed concordant result. The incidence of injection site re-

actions in the low-dose group was significantly lower, and the incidence of other adverse events showed no differences

between the two groups. In the low-dose group, dose reduction after more than 24 weeks of standard-dose treatment was

associated with longer drug survival (adjusted HR=0.261, 95% CI 0.084-0.809).

Conclusion: Low-dose etanercept treatment after achieving clinical remission can be an alternative treatment option

in terms of its comparable long-term efficacy and favorable safety in AS. More than 24 weeks of standard-dose treatment

before dose reduction may be beneficial for longer drug survival in this strategy.

(2010. 1. 1∼2010. 12. 31)


Research Society Session on Spondyloarthritis

2부 - 강직성 척추염 NEWs and Updates


S151

Clinical Update on Spondyloarthritis

이연아

경희대학교 의과대학 류마티스내과

이연아: Clinical Update on Spondyloarthritis



S158

척추관절염 Update: Basic and Translational Research

이상훈

강동경희대병원 류마티스내과

이상훈: 척추관절염 Update: Basic and Translational Research


(2010. 1. 1∼2010. 12. 31)


Free Paper Session: Systemic Lupus

Erythematosus Clinical Aspects


S165

Effects of Risk Factors for Metabolic Syndrome and the Components of Metabolic Syndrome on the Quality of Life of Patients with Systemic Lupus Erythematosus:

A Structural Equation Modeling Approach

Jeong-Won Lee, Ji-Hyoun Kang, Yi-Rang Yim, Ji-Eun Kim, Kyung-Eun Lee, Lihui Wen, Dong-Jin Park, Tae-Jong Kim, Yong-Wook Park, Shin-Seok Lee

Devision of rheumatology, Department of Internal Medicine, Chonnam National University Medical School and Hospital, Gwangju, Korea

Objectives: This study assessed 1) relationships among risk factors for metabolic syndrome (MS), components of MS,

and health related quality of life (HRQOL), and 2) the effects of these variables on HRQOL in a hypothesized causal mod-

el using structural equation modeling (SEM) in Korean patients with systemic lupus erythematosus (SLE).

Methods: Of the 505 patients with SLE enrolled in the Korean Lupus Network (KORNET registry), we investigated

244 patients with sufficient data to assess the components of metabolic syndrome at the time of cohort entry. We eval-

uated the education, income, corticosteroid dose, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI),

Physicians Global Assessment (PGA), depression, components of metabolic syndrome, and HRQOL at the time of cohort

entry. SEM was used to test the structural relationships of the model using AMOS software ver. 23.

Results: The 244 patients had an average age of 40.7±11.8 years and included 228 (93.4%) women. The SEM results

supported the good fit of the model (χ2=71.629, df=56, p=0.078, RMSEA 0.034, CFI 0.972). The final model showed

that higher education and income had a direct negative effect on MS and higher disease activity had a positive indirect

effect on MS as mediated by the corticosteroid dose. Higher education and income had indirect effects on HRQOL, and

higher disease activity had a direct negative effect on HRQOL. MS had no direct impact on HRQOL, but an indirect neg-

ative impact on HRQOL as mediated by depression.

Conclusion: In our causal model, risk factors for MS were related to MS, directly and indirectly. MS had a negative in-

direct impact on HRQOL as mediated by depression. Therefore, clinicians should consider socioeconomic status, medi-

cation, and depression and try to modify the disease activity and metabolic syndrome, to improve the HRQOL of SLE

patients.

O-21-10


S166

Factors Related to Blood Hydroxychloroquine Concentration in Patients with Systemic Lupus Erythematosus

Ji Yeon Lee, Seung Ki Kwok, Ji Hyeon Ju, Kyung Su Park, Sung-Hwan Park

Division of Rheumatology, Department of Medicine, Catholic University of Korea, Seoul St.Mary’s Hospital, Seoul, Korea

Objective: To identify factors associated with blood concentrations of hydroxychloroquine (HCQ) and its major metab-

olite, N-desethylhydroxychloroquine (DHCQ), in patients with systemic lupus erythematosus (SLE) receiving

long-term oral HCQ treatment.

Methods: SLE patients who had been taking HCQ for more than 3 months were recruited. Various clinical character-

istics, laboratory values, and SLE disease activity index (SLEDAI) scores were examined. The concentration of HCQ and

DHCQ ([HCQ] and [DHCQ]) was measured by liquid chromatography-mass spectrometry, and the relationship be-

tween [HCQ], [DHCQ], and the ratio of the two to various factors was investigated.

Results: In total, 189 SLE patients on long-term HCQ treatment were included in the analysis. The mean [HCQ] was

589.3±360.7 ng/ml, the mean [DHCQ] was 460.5±299.9 ng/ml, and the value for [HCQ]/[DHCQ] was 1.45±0.7.

[HCQ] was closely associated with [DHCQ] (r=0.88, p<0.0001). The weight-adjusted oral HCQ dose was strongly asso-

ciated with both [HCQ] (p<0.001) and [DHCQ] (p<0.001). Unadjusted and adjusted models revealed no significant as-

sociation between renal function and [HCQ] or [DHCQ]. Additional use of immunosuppressants increased [DHCQ] af-

ter adjusting for possible confounders (p=0.04). The prednisolone dose was associated with a higher [HCQ]/[DHCQ]

value (p=0.02-0.03), and the lower SLEDAI score was significantly related to higher [HCQ] after adjusting for con-

founders (p=0.002-0.008).

Conclusion: Various factors affect [HCQ], [DHCQ], or the [HCQ]/[DHCQ] value in the blood of SLE patients on

long-term oral HCQ treatment. Notably, a higher [HCQ] was associated with a lower SLEDAI score, even when [HCQ]

was less than 1,000 ng/ml.

O-21-11


S167

Factors Influencing on Health-Related Quality of Life in Korean Patients with Systemic Lupus Erythematosus

Su-Jin Moon1, Kwi Young Kang1, Seung-Ki Kwok1, Ji Hyeon Ju1, Wan-Uk Kim1, Yeon-Sik Hong1, Sung-Hwan Park1, Chan Hong Jeon2, Sang Tae Choi3, Jung-Soo Song3, Jun-Ki Min1

1Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, 2Division of Rheumatology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, 3Division of Rheumatology, Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea

Background: Health-related quality of life (HRQoL) among SLE patients is reduced, because SLE can significantly im-

pact both physiological and psychological functioning. With the advent of new treatment and better understanding of the

disease, survival has improved in recent decades. However, this has not translated into improvement in HRQoL. To im-

prove the HRQoL in SLE patients, it might be the clinically important and constructive theme to investigate that which

is the most important factor among the fibomyalgia, depression, sleep quality, SLE activity and SLE duration.

Objectives: To evaluate the contributing factors for reduced HRQoL for reduced HRQoL in Korean female patients with

SLE.

Methods: Subjects were selected from the five affiliated hospitals in South Korea. This prospective study included 152

Korean female patients with SLE and 139 age, and sex-matched healthy controls.

Results: SLE patients fared significantly worse than age matched controls. Forty-one patients with SLE had

fibromyalgia. The education level was lower in FMS group (p value<0.05). The overall quality of life was lower in patients

that had FMS. Sleep quality was assessed using the Pittsburg Sleep Quality Index (PSQI). Global PSQI was also higher,

indicating the poorer sleep quality in SLE patients with FMS, as compared with those without FMS. SLE disease activity

as assessed by SELENA-SLEDAI score was significantly higher in FMS group, whereas SLICC-ACR damage index did not

differ between the two groups. SLE disease duration and mean steroid dose did not show statistical significance between

the two groups. In SLE patients without FMS, fatigue severity and poor perceived sleep quality negatively influence qual-

ity of life in patients with SLE. In SLE patients with FMS, fatigue severity and SLE disease damage index independently

influence the decreased quality of life.

Conclusion: The poorer quality of life in SLE patients can be improved by fatigue manage and improving sleep quality.

O-21-12


S168

Corticosteroids Dose After 6 Months of Induction Therapy is Associated with Non-Renal Organ Damage in Patients with Lupus Nephritis

Chan-Bum Choi1, Young Bin Joo1, Soyoung Won2, Sang-Cheol Bae1

1Hanyang University Hospital for Rheumatic Diseases, 2Clinical Research Center for Rheumatoid Arthritis, Seoul, Korea

Background: Lupus nephritis (LN) is one of the most common and serious organ involvement and long-term cortico-

steroids, especially at high doses, used for its treatment can cause organ damage. Failure to taper can cause increase in

damage either by high disease activity preventing the taper or the corticosteroids itself.

Objectives: We investigated the relationship between the corticosteroids dose after 6 months of induction therapy and

organ damage.

Methods: Corticosteroids dose at 6 months after induction were assessed in patients with LN. Patients who tapered

the corticosteroids to ≤10 mg/d and those who failed to taper to 10 mg/d were compared on demographic characteristics

and SLE-related characteristics..

Results: A total of 166 patients, including 66 patients with corticosteroids dose tapered to ≤10 mg/d at 6 months after

induction and 100 patients who failed to taper to 10mg/d were analyzed. There were no significant differences in baseline

demographic and SLE-related characteristics. Patients who failed to taper corticosteroids to 10 mg/d after 6 months of

induction therapy were on higher doses of corticosteroids, had higher proportion of patients with SDI ≥1, and higher

cumulative SDI score. Patients who failed to taper were more likely to have both renal and non-renal organ damage (renal

damage OR 2.38, 95% CI 1.16-4.85; non-renal damage OR 16.0, 95% CI 1.99-128.1). In multivariate regression analysis

adjusted for age, sex, disease duration, AMS, and induction treatment regimen, corticosteroids dose of >10 mg at 6

months of induction therapy was associated with non-renal damage (OR 112.15, 95% CI 4.04-99.9), but not with renal

damage (OR 2.13, 95% CI 0.95-4.77).

Conclusion: Failing to taper corticosteroids to ≤10 mg at 6 months of induction therapy is associated with non-renal

organ damage in patients with lupus nephritis.

O-21-13


S169

Improved Survival of Systemic Lupus Erythematosus Patients with Rituximab Treatment

Na Ri Kim, Jung Su Eun, Jong Wan Kang, Eon Jeong Nam, Young Mo Kang*

Division of Rheumatology, Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea

Background: Systemic Lupus Erythematosus (SLE) is an autoimmune disease with diverse clinical manifestations in

multiple organ systems. Although two recent randomized controlled trials of rituximab in SLE showed no significant

beneficial effects, rituximab has proven optimistic results in several open label trials.

Objectives: We report a retrospective study to evaluate the efficacy of rituximab in the treatment of moder-

ately-to-severely active SLE.

Methods: We enrolled 46 SLE patients treated with immunosuppressive regimen including rituximab. The control

group consisted of 46 SLE Disease Activity Index (SLEDAI)-matched patients who had not received rituximab treatment.

Clinical and laboratory measures of disease activity, immunosuppressive regimen, infection and survival rates were

assessed.

Results: Baseline disease activity and organ involvement were similar in the rituximab and control groups with mean

SLEDAI score of 23.8 and 23.0, respectively at baseline and 3.2 and 4.5, respectively at 36 months of follow-up. Although

the infection rates were lower in the rituximab group (50.0% vs. 82.2% in control group, P=0.002), a significant differ-

ence was not observed in severe infection rates (50.0% vs. 67.4%, P=0.138). Steroid sparing effect was shown in ritux-

imab group (P=0.007). The survival rates were significantly higher in the rituximab group compared with control group

(91.3% vs. 72.7%, P=0.028).

Conclusion: Rituximab have superior efficacy in reducing steroid dosage and improving mortality in moderate to se-

vere SLE patients compared with immunosuppressive regimen without rituximab. A prospective study evaluating the

outcome of rituximab treatment in moderately-to-severely active SLE is warranted.

O-21-14

(2010. 1. 1∼2010. 12. 31)


Free Paper Session: Osteoporosis, Gout,

Cytokines


S173

Glucocorticoid Acts Differently on Vertebral and Hip Fractures in Korean RA Patients Using

National Healthcare Claims Database

Dam Kim1,2, Soo-Kyung Cho1,2, Byeongju Park3, Eun Jin Jang4, Sang-Cheol Bae1,2, Yoon-Kyoung Sung1,2

1Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, 2Clinical Research Center for Rheumatoid Arthritis (CRCRA), Seoul, 3Department of Statistics, Kyungpook National University, Daegu,

4Department of Information Statistics, Andong National University, Andong, Korea

Background: Fracture in rheumatoid arthritis (RA) patient is more frequent than general population. One of the im-

portant reasons is use of glucocorticoid (GC) for treatment of RA.

Objectives: In this study, we aimed to identify the effect of GC on fracture of different site.

Methods: Among RA patients ≥19 years, we established a retrospective cohort using Korean national healthcare

claims database from Jan 2010 to Dec 2010, and then followed up until Dec 2013. RA patients who experienced fracture

in year 2009 were excluded. Fractures were identified on the basis of selected ICD-10 codes and information about clinic

visit until last visit. Information about oral GC use was collected until incidence of fracture or last visit. In multivariable

logistic regression analysis, each of variables such as duration, mean dose, and highest daily dose of GC were adjusted

for age, gender, payer type, type of institution, physician’s specialities, comorbidities and medication.

Results: The 11,599 fractures in 9,964 RA patients were observed among total of 138,240 RA patients. The 68.19%

of patients used oral GC more than 3 months. Mean dose of GC was 6.1±4.7 mg and their highest daily dose was

16.20±15.8 mg. In adjusted analysis, duration of GC≥6 months (OR 1.36, p<0.01 for total fracture; OR 1.76, p<0.01

for vertebral fracture), mean dose of GC≥2.5 mg (OR 1.17-1.34, p<0.01 in total fracture; OR 1.37-1.71, p<0.01 in verte-

bral fracture) and highest daily dose of GC≥10 mg (OR 1.22-1.33, p<0.01 in total fracture; OR 1.23-1.75, p<0.03 in ver-

tebral fracture) increased the risk of total and vertebral fracture. However, in hip fracture, neither duration nor dose of

oral GC increased the risk.

Conclusion: Use of oral GC increased the risk of total and vertebral fracture, however, it did not increase the risk of

hip fracture in RA patients.

O-21-15


S174

Ebselen is a Potential Anti-Osteoporosis Agent by Suppressing Receptor Activator of NF-κB Ligand-Induced

Osteoclast Differentiation and LPS-Induced Inflammatory Bone Destruction

Changhoon Lee1, Jong Min Baek2, Ju-Young Kim2, Jaemin Oh2, Myeung-Su Lee1

1Division of Rheumatology, Department of Internal Medicine, Wonkwang University Hospital, 2Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Korea

Ebselen is a non-toxic seleno-organic drug with anti-inflammatory and antioxidant properties.

We investigated the effects of ebselen on RANKL-induced differentiation of osteoclasts and their functions and the un-

derlying molecular mechanisms. Furthermore, we determined the effects of ebselen on LPS-induced bone erosion in

vivo.To generate osteoclasts from BMMs, we cultured BMMs for 4 days pretreated with ebselen. The cells were then

stained with rhodamine-conjugated phalloidin for F-actin ring labeling and DAPI solution to detect apoptotic body

formation. The change of F-actin ring on mature osteoclasts induced by ebselen was quantified by calculating the ratio

of actin ring positive (AR+) osteoclasts versus AR-. To detect the formation of apoptotic osteoclasts, we performed

TUNEL assay. ICR mice were divided into phosphate-buffered saline-treated (control) group, ebselen only-treated

group, LPS only-treated group, and LPSand ebselen-treated group. Micro-computed tomography data containing 3D im-

ages and bone parameters and histological data were acquired. Ebselen suppressed the formation of multinucleated cells

by regulating the ratio of RANKL/osteoprotegerin. Ebselen treatment in the early stage inhibited osteoclastogenesis by

decreasing the phosphorylation of IκB, PI3K, and Akt in early signaling pathways. Ebselen induced apoptosis of osteo-

clasts in the late stage.Ebselen treatment suppressed filamentous actin ring formation and bone resorption activity.

Administration of ebselen recovered bone loss and its μ-CT parameters in LPS-mediated mouse model. Histological

analysis confirmed that ebselen prevented trabecular bone matrix degradation and osteoclast formation in the bone

tissues. Finally, it was proved that the anti-osteoclastogenic action of ebselen is achieved through targeting N-meth-

yl-D-aspartate receptor.

O-21-16


S175

p62 is Responsible for Interleukin-1β Production at the Early Phase through Mitochondrial Apoptosis

by Monosodium Urate Crystals

Seong-Kyu Kim, Jung-Yoon Choe, Ji Na Kim, Ji-Won Kim, Chan Uk Lee

Division of Rheumatology, Department of Internal Medicine, Arthritis and Autoimmunity Research Center Catholic University of Daegu School of Medicine, Daegu, Korea

Objective: The aim of this study was to clarify the role of p62-dependent mitochondrial apoptosis in the initiation of

monosodium urate (MSU) crystal-induced inflammation in macrophages.

Methods: The induction of mitochondrial apoptosis in RAW 264.7 murine macrophages by MSU crystals was meas-

ured using western blotting and quantitative real-time polymerase chain reaction for Bax, caspase-3, caspase-9, or

PARP1, and by flow cytometric analysis. Immunoprecipitation and western blotting was applied to detect ubiquitination

of p62, TRAF6, and caspase-9. Mitochondrial apoptosis, reactive oxygen species (ROS) generation, and cell proliferation

were assessed in cells transfected with p62 siRNA.

Results: Treatment of RAW 264.7 cells with MSU crystals induced activation of Bax, caspase-3, caspase-9, and PARP1

at the early phase, in addition to enhancing IL-1β expression, but these findings were attenuated at the late phase. MSU

crystals induced ubiquitination of p62, followed by ubiquitination of TRAF6 and caspase-9, which were significantly re-

versed by ascorbic acid. RAW 264.7 cells transfected with p62 siRNA showed attenuated expression of Bax, caspase-3,

caspase-9, and PARP1, decreased ROS and IL-1β production, and increased cell proliferation, compared to controls. The

antioxidant ascorbic acid inhibited p62, caspase-9, and IL-1β expression increased by MSU crystals.

Conclusion: p62 may be a crucial mediator for the mitochondrial apoptosis pathway in MSU crystal-induced in-

flammation, which is linked to the acute inflammatory response during the early phase of gout.

O-21-17


S176

SIRT-1 Regulates TGF-β Induced Dermal Fibroblast Migration Via Modulation of Cyr61 Expression

Eun-Jeong Kwon1, Eun-Jung Park2, Moonjae Cho3, Jinseok Kim1,2*1Department of Medicine, Jeju National University School of Medicine, 2Departmnet of Internal Medicine,

3Department of Biochemistry, Jeju National University School of Medicine, Jeju, Korea

Background: SIRT1 is a NAD-dependent protein deacetylase that participate in cellular regulation. A key feature for

activation of fibroblast is increased migration and uncontrolled activation of fibroblasts lead to produce pathologic con-

dition such as systemic sclerosis, kidney fibrosis and idiopathic pulmonary fibrosis. The role of SIRT1 in human dermal

fibroblasts (HDFs) migration remains unknown.

Objectives: The aim of this study was to establish the role of SIRT1 in HDFs migration and explore a target of SIRT1

for HDF migration.

Methods: Levels of SIRT1 expression were analysed in HDFs by RT-PCR and western blotting before and after stim-

ulation with TGF-β and resveratol (RSV). HDFs were transfected with active SIRT1 expression vectors or with siRNA

targeting SIRT1 or were treated with nicotinamide (NAM). Cyr61 expression analysis was performed by western blotting

to study the role of SIRT1 on cell migration. The wound healing assay was performed due to analyze migration of HDFs.

Results: SIRT1 and Cyr61 was expressed in HDFs and the stimulation of TGF-β further induced expression levels of

SIRT1 and Cyr61. Treatment of RSV, SIRT1 agonist or overexpression of SIRT1 also promoted expression of SIRT1 and

Cyr61 in HDFs, whereas inhibition of SIRT1 activity by NAM or knock down of SIRT1 down-regulated Cyr61 basal level

as well as TGF-β or RSV-induced Cyr61expression. Blocking of ERK signaling by PD98509 reduced TGF-β or RSV-in-

duced Cyr61 expression. SIRT-1-dependent β-catenin also modulated Cyr61 expression. RSV increased migration and

NAM attenuated RSV-induced migration of HDFs. Furthermore, SIRT1 overexpression promoted cell migration whereas

blocking Cyr61 attenuated SIRT1-stimulated migration of HDFs.

Conclusion: We suggested a role of SIRT1 in HDFs migration. SIRT1 increased cell migration by stimulated Cyr61 ex-

pression for their target through the ERK and β-catenin/Wnt signaling. SIRT1-induced Cyr61 production is important

for HDFs migration.

O-21-18

(2010. 1. 1∼2010. 12. 31)


Poster Presentation


S179

The Synovial Fluid Concentrations of Cold-inducible RNA-binding Protein are Correlated with Disease Activity in

Patients with Rheumatoid Arthritis

In Seol Yoo, Young Kim, Seong Wook Kang, Seung-Cheol Shim, Jinhyun Kim, Su-Jin Yoo, Sun Young Lee, Chan Keol Park

Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Korea

Background: The cold-inducible RNA-binding protein (CIRP) is 18 kDa protein of the glycine-rich RNA binding pro-

tein (GRP) family, and is upregulated during mild hypothermia, UV exposure and hypoxia. In recent studies, extracellular

CIRP is a recently identified endogenous proinflammatory mediator and damage-associated molecular pattern molecules

(DAMP) that triggers inflammatory responses in sepsis and inflammatory bowel disease.

Objectives: This study was planned to investigate the relationship between CIRP and rheumatoid arthritis.

Methods: Peripheral blood and synovial fluid were collected from 15 patients with rheumatoid arthritis (RA) and 16

patients with osteoarthritis (OA). The concentration of CIRP was measured by sandwich ELISA.

Results: The concentration of serum CIRP was significantly elevated in RA patients group (RA patients=26.39±10.48

pg/ml, OA patients=17.14±7.24 pg/ml, p=0.009). Furthermore, the RA patients group showed significantly higher

CIRP concentration than the OA patients group in synovial fluid (153.56±108.93 pg/ml vs. 23.63±16.18 pg/ml,

p<0.001) (Fig. 1). The mean concentration of synovial fluid CIRP was significantly higher than that of serum in RA pa-

tients group (Serum concentration=26.39±10.48 pg/ml, Synovial fluid=153.56±108.93 pg/ml, p<0.001). Also, the

synovial concentration of CIRP was significantly increased in the treatment-naïve group (treatment-naïve group=

223.22±52.05, DMARDs treatment-experienced group=107.13±114.06, p=0.02) (Fig. 2). DAS28-ESR and DAS28-

CRP were positively correlated with synovial fluid concentration of CIRP (DAS28-ESR: r=0.582, p=0.023, DAS28-CRP:

r=0.541, p=0.037).

Conclusion: The serum and synovial concentration of CIRP in RA patients was increased compared to OA patients.

Also synovial concentration of CIRP in RA patients correlated well with the disease activity, i.e. the DAS28-ESR/CRP.

Based on these results, the CIRP mediates the inflammation and is potential marker for synovial inflammation.

Poster 1


S180

A Role of Synovial Exosomes in Osteoclast Differentiation of Inflammatory Arthritis

Ji Eun Song1, Ji Hye Shin1, Ki Won Moon2, Se Hui Shon1, Ji Soo Park3, Eun Bong Lee3, Yeong Wook Song1,3, Eun Young Lee3*

1Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, 2Department of Internal Medicine, Kangwon National University Hospital, Chuncheon,

3Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea

Background: Exosomes are small membrane vesicles (40-150 nm) of endocytic origin secreted by many types of cells

and engage in cell-to-cell communication by transferring proteins, microRNAs, and lipid to recipient cells. Exosomes are

also identified in various biological fluids. Until now, the role of exosomes from synovial fluid (SF) on human osteoclasto-

genesis is unknown.

Objectives: We aimed to identify the characteristics of synovial exosomes and evaluate the effects on human

osteoclastogenesis.

Methods: Synovial exosomes were isolated from SF of rheumatoid arthritis (RA), osteoarthritis (OA), ankylosing

spondylitis (AS), and gout patients using ExoQuick. Monocytes were isolated from human peripheral blood mono-

nuclear cell and were differentiated into macrophages. Then, macrophages were incubated with synovial exosomes for

9-10 days. Osteoclast differentiation was evaluated by tartrate resistant acid phosphatase stain. Exosomes from RA

(n=11), OA (n=5), AS (n=6), and gout (n=6) patients were quantified by measuring acetylcholinesterase activity.

Results: We found that exosomes are abundant in SF of RA, AS, and gout patients compared to OA patients.

Interestingly, the number of exosomes from AS SF was significantly higher than exosomes from OA SF (p=0.0476).

Exosomes isolated from SF induced proliferation and osteoclast formation without macrophage colony-stimulating fac-

tor and receptor activator of nuclear factor kappa-B ligand. Noticeably, exosomes from RA SF had higher potential on os-

teoclast differentiation than other three diseases.

Conclusions: Our results suggest that exosomes from SF of various inflammatory diseases might have differential

functional roles in osteoclast differentiation and the number of exosomes may be associated with inflammatory

conditions.

Poster 2


S181

The Relationship between the Articular Surface Projection and Radiologic Laxity of the Trapeziometacarpal Joint

Jeong Hwan Kim1, Hyun Sik Gong2, Jihyeung Kim2, Goo Hyun Baek2

1Department of Orthopedic Surgery, Seoul Medical Center, Seoul, 2Department of Orthopedic Surgery, Seoul National University College of Medicine, Seoul, Korea

Background: Trapeziometacarpal joint (TMCJ) osteoarthritis is a common disorder related with the aging process, with

reported prevalence of 25% in postmenopausal women and 94~100% in women older than 80 years. And hypermobility

of the TMCJ is considered as one of the causes of TMCJ osteoarthritis.

Objectives: We aimed to determine whether the articular surface projection was associated with hypermobility of the

TMCJ.

Methods: We evaluated 108 women without TMCJ osteoarthritis or generalized ligament laxity which was defined by

the scores of ≥4 in the Beighton and Horan scale. We assessed the first metacarpal base articular slope and the trapezial

tilt in radiographs. And we assessed the radiologic laxity of TMCJ using the subluxation ratio in a TMCJ stress view. We

compared radiologic laxity of the TMCJ using subluxation ratio with regard to the metacarpal slope or the trapezial tilt.

Results: The mean trapezial tilt was 38 degrees and the mean metacarpal base articular slope was 82 degrees. And the

mean subluxation ratio was 0.27. After dividing the subjects into four subsets according to metacarpal slope, there was

a statistically significant difference in the mean subluxation ratio those in the upper and lower quartiles of the metacarpal

slope (0.24 vs 0.32, P=0.013). However, there was no difference in the subluxation ratio with regard to the trapezial tilt

(0.29 vs 0.24, P=0.189).

Conclusion: This study suggests that a steeper articular slope of the first metacarpal base could be associated with the

radiologic laxity of the TMCJ. Further longitudinal studies are necessary to determine whether this anatomic difference

represents a risk factor for later development of TMCJ osteoarthritis.

Poster 3


S182

Impact of Myofascial Pain Syndrome on Pain and Functional Status in Patients with Hand Osteoarthritis

Young Sun Suh1, Yun-Hong Cheon2, Hyun-Ok Kim1, Rock-Bum Kim3, Ki Soo Park3, Hyung Bin Park4, Jae-Bum Na5, Sang-Il Lee2

1Division of Rheumatology, Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Changwon, 2Division of Rheumatology, Department of Internal Medicine, 3Preventive Medicine, 4Orthopedic Surgery, 5Radiology,

Gyeongsang National University School of Medicine, Jinju, Korea

Background: Various upper extremity musculoskeletal diseases (MSDs) can affect pain and disability in patients with

hand osteoarthritis (HOA). However, there was no previous study investigating the relationship between upper ex-

tremity MSDs and HOA.

Objectives: To explore the influence of major upper extremity MSDs on pain severity and functional status of patients

with HOA.

Methods: We enrolled 1150 inhabitants in Gyeongnam province in Korea from June 2013 to December 2015. Physical

examinations were performed by rheumatologists, orthopedists, and rehabilitation specialists. Grip powers of both

hands also were evaluated. Plain radiography, a nerve conduction velocity (NCV) examination, and magnetic resonance

imaging (MRI) of shoulders were performed. The Australian/Canadian Osteoarthritis Hand Index (AUSCAN) was used

to assess pain severity and functional status of hand joints. The diagnosis of HOA was made by the 1990 American

College of Rheumatology classification criteria. Carpal tunnel syndrome (CTS) was confirmed by NCV findings, and rota-

tor cuff tear (RCT) was diagnosed by MRI findings. Myofascial pain syndrome (MPS) was diagnosed by palpations of my-

ofascial trigger points.

Results: Of 1150 participants, 307 were diagnosed with HOA. Among HOA patients, 151 (49.7%), 192 (62.5%), and

249 (80.1%) patients had CTS, RCTs, and MPS, respectively. HOA patients with MPS showed significantly higher

AUSCAN scores (350.4±285.0 vs 200.4±201.8, p<0.001) and decreased grip power of a dominant hand (22.5±9.8 vs.

26.2±9.8, p=0.011) compared with HOA without MPS. Linear regression analysis also showed that MPS was associated

with AUSCAN scores after adjustment for age and gender (β=0.21, p=0.001). The existence of CTS or RCT did not in-

fluence on AUSCAN scores and grip power.

Conclusions: Therefore, management of coexisting MPS is the better way to improve pain and function of hand joints

in patients with HOA.

Poster 4


S183

The Value of High-sensitivity C-reactive Protein in Hand and Knee Radiographic Osteoarthritis:

Data from the Dong-gu Study

Yi-Rang Yim, Lihui Wen, Ji-Hyoun Kang, Ji-Eun Kim, Jeong-Won Lee, Kyung-Eun Lee, Dong-Jin Park, Tae-Jong Kim, Yong-Wook Park, Sun-Seog Kweon, Young-Hoon Lee, Yong-Woon Yun, Min-Ho Shin, Shin-Seok Lee

Department of Rheumatology, Chonnam National University Hospital & Medical School, Gwangju, Korea

Objective: We evaluated whether high-sensitivity C-reactive protein (hs-CRP) was related to various radiographic

findings in older adults with osteoarthritis (OA) because of the inconsistent association between hs-CRP and OA.

Methods: This cross-sectional study recruited 2,376 participants from the population-based Dong-gu cohort. The

scores of radiographic features in OA on x-rays of the knees and hands were computed using a semi-quantitative grading

system. The hs-CRP levels were measured using a particle-enhanced immunonephelometry assay. Correlations showing

the relationship between hs-CRP and OA were calculated using multiple linear correlation analysis.

Results: The hs-CRP levels were significantly higher in older subjects (p<0.001), those with a higher Body Mass Index

(BMI) (p<0.001), current smokers (p<0.001), current alcohol drinkers (p=0.014), those who engaged in less physical

activity (p=0.003), and those with a lower level of education (p=0.040). After adjusting for BMI and other confounders,

the total OA scores (knee, p=0.048; hand, p=0.010), erosion scores (knee, p=0.035; hand, p=0.031), and sclerosis

(knee, p=0.021; hand, p=0.029) in the knees and hands were all significantly positively correlated with hs-CRP. A sig-

nificant association was also observed between hs-CRP and the hand malalignment score (p=0.012).

Conclusions: In this large cross-sectional study, the hs-CRP level was a significant predictor of radiographic OA. Of the

types of OA radiographic damage, erosion, sclerosis, and malalignment showed significant associations with hs-CRP.

Poster 5


S184

Leptin Protects Rat Articular Chondrocytes from TNF-α Cytotoxicity Induced by Cyclohexamide

Sang Yeob Lee, Sung Won Lee, Won Tae Chung

Department of Rheumatology, Division of Internal Medicine, Dong-A Uiversity

Objective: Although leptin appears to be an important local and systemic factor influencing cartilage homeostasis, the

role of leptin in chondrocyte death is largely unknown. Tumor necrosis factor a (TNF-a) is a pro-inflammatory cytokine

that plays a central role in the pathogenesis of articular diseases. This study examines whether leptin modulates

TNF-a-induced articular chondrocyte death.

Methods: Primary rat articular chondrocytes were isolated from knee joint cartilage slices. To induce cell death, the

chondrocytes were treated with TNF-a. To examine whether leptin modulates the extent of TNF-a-mediated chondrocyte

death, the cells were pretreated with leptin for 3 h before TNF-a treatment followed by viability analysis. To examine the

mechanism by which leptin modulates the extent of TNF-a-mediated chondrocyte death, we utilized mitochondrial

membrane potential (MMP) measurements, flow cytometry, nuclear morphology observation, co-immunoprecipitation,

western blot analysis and confocal microscopy.

Results: We demonstrated that leptin suppresses TNF-a induced chondrocyte death. We further found that apoptosis

partially contributes to TNF-a induced chondrocyte death while necroptosis primarily contributes to TNF-a induced

chondrocyte death. In addition, we observed that leptin exerts anti-TNF-a toxicity via c-jun N-terminal kinase (JNK) in

rat articular chondrocytes.

Conclusion: Based on our findings, we suggest that the leptin present in the articular joint fluid protects articular chon-

drocytes against cumulative mechanical load and detrimental stresses throughout a lifetime, delaying the onset of degen-

erative changes in chondrocytes. We can further hypothesize that leptin protects articular chondrocytes against destruc-

tive stimuli even in the joints of osteoarthritis (OA) patients.

Poster 6


S185

Association-heterogeneity Mapping Identifies an Asian-specific Association of the GTF2I Locus

with Rheumatoid Arthritis

Kwangwoo Kim1, So-Young Bang1, Katsunori Ikari2,3, Dae Hyun Yoo1, Soo-Kyung Cho1, Chan-Bum Choi1, Yoon-Kyoung Sung1, Tae-Hwan Kim1, Jae-Bum Jun1, Young Mo Kang4, Chang-Hee Suh5, Seung-Cheol Shim6,

Shin-Seok Lee7, Jisoo Lee8, Won Tae Chung9, Seong-Kyu Kim10, Jung-Yoon Choe10, Shigeki Momohara2, Atsuo Taniguchi2, Hisashi Yamanaka2, Swapan K Nath11, Hye-Soon Lee1, Sang-Cheol Bae1

1Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea, 2Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, 3Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Tokyo, Japan, 4Division of Rheumatology, Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, 5Department of Rheumatology, Ajou University School of Medicine, Suwon, 6Division of Rheumatology, Daejeon Rheumatoid & Degenerative Arthritis Center, Chungnam National University Hospital, Daejeon, 7Division of Rheumatology, Department of Internal Medicine, Chonnam National University

Medical School and Hospital, Gwangju, 8Division of Rheumatology, Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, 9Division of Rheumatology, Department of internal medicine, Dong-A University, Busan, 10Division of Rheumatology,

Department of Internal Medicine, Arthritis & Autoimmunity Research Center, Catholic University of Daegu School of Medicine, Daegu, Korea, 11Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA

Background: Genetic association studies using multiple ancestral cohorts have revealed a large overlap of rheumatoid

arthritis (RA)-risk alleles among different ancestries, but there are some exceptional loci showing heterogenic associa-

tion among populations.

Objectives: Here we investigated genetic variants with distinct effects on the development of RA in Asian and

European populations.

Methods: Ancestry-related association heterogeneity was examined using the association data from large Korean

(n=9,299) and European (n=45,790) rheumatoid arthritis cohorts with Immunochip and genome-wide SNP array data.

Novel disease associations detected in Koreans were validated using two independent Asian cohorts (n=5,166) and a

meta-analysis.

Results: We identified significant heterogeneity between the two ancestries for the common variants in the GTF2I lo-

cus and showed that this heterogeneity is due to an Asian-specific association effect (PHeterogeneity=9.6×10-9 at rs73366469

[ORMeta=1.37 and PMeta=4.2×10-13 in Asians; ORMeta=1.00 and PMeta=1.00 in Europeans]) in RA. Trans-ancestral com-

parison and bioinfomatics analysis revealed a plausibly causal SNP (rs117026326; linked to rs73366469), whose minor

allele is common in Asians but rare in Europeans.

Conclusion. We identified the largest effect on Asian RA across human non-HLA regions at GTF2I by heterogeneity

mapping followed by replication studies, and pinpointed a possible causal variant.

Poster 7


S186

Stauntonia Hexaphylla Extract Suppresses Expression of Pro-inflammatory Mediators, MMPs through Downregulating Akt, p38, JNK and NF-κB Activation in

Rheumatoid Arthritis Fibroblast-like Synoviocytes

Hyung Jung Yoo1,2, Jeong Yeon Kim1,2, Shin Eui Kang1,2, Ji Soo Park2, Eun Young Lee2, Eun Bong Lee2, Yeong Wook Song1,2

1Department of Molecular Medicine and Biopharmaceutical Science, Medical Research Center, Graduate School of Convergence Science and Technology and College of Medicine, Seoul National University, Seoul,

2Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea

Natural plants, including common vegetables and fruits, have been recognized as essential sources for drug discovery

and the development of new, safe, and economical medicaments. Stauntonia hexalphylla (Lardizabalaceae) is widely dis-

tributed in Korea, Japan and China, and is a popular herbal supplement in Korean and Chinese folk medicine owing to

its analgesic, sedative, and diuretic properties. However, the exact pharmacological effects of S. hexaphylla extract, partic-

ularly its effect on inflammation, are not known.

We investigated the suppressive effect of S. hexaphylla extract, YRA-1909 on lipopolysaccharide (LPS) - induced ex-

pression of pro-inflammatory mediators and the molecular mechanisms underlying these activity in rheumatoid arthritis

fibroblast-like synoviocytes (RA-FLS). YRA-1909 inhibited the production of pro-inflammatory cytokines, chemokines

and matrix metalloproteinases (MMPs) including tumor necrosis factor-α, interleukin-6 (IL-6), IL-17A, CXCL8,

CXCL10, MMP-1, 2, 3, 9 and 13 in RA-FLSs. Moreover, YRA-1909 suppressed LPS-induced nitric oxide reduced the ex-

pression of cyclooxygenase-2, as well as a reduction in MMP-2 gelatinolytic activity in RA-FLSs. YRA-1909 suppressed

LPS-induced phosphorylation Akt and mitogen-activated protein kinases (MAPKs), including JNK1/2, and p38

signaling. Furthermore, YRA-1909 inhibited LPS-induced nuclear factor kappa B (NF-κB) activation by reducing the

phosphorylation of p65 at Ser468 and Ser536. YRA-1909 also suppressed nucleus translocation of p65.

These observations suggest that S. hexaphylla might be useful for the development of new anti-inflammatory agents.

Poster 8


S187

Hypoxia Induce Slug Expression Via JAK/STAT3 Pathway in Rheumatoid Arthritis Fibroblast-like Synoviocytes

Hyungjin Kim1, Hyemin Jeong1, Jaejoon Lee1, Hoon-Suk Cha1, Eun-Mi Koh1, Joong Kyong Ahn2

1Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 2Department of Internal Medicine, Division of Rheumatology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea

Background: Accumulating evidence implicates hypoxia in the pathogenesis of RA. The effect of hypoxia on the ex-

pression of Slug, a transcriptional repressor that impairs apoptosis of RA FLS, remains unknown.

Objectives: The aim of this study is to investigate the role of hypoxia in the expression of Slug in RA FLS and to delin-

eate the signaling pathway involved in the process.

Methods: After RA FLS were exposed to hypoxia, expression of HIF1-α and phosphorylation of ERK, JNK, and STAT3

were analyzed by Western blot. The experiment was repeated with RA FLS pretreated with WP1066, an inhibitor of the

JAK/STAT pathway. RT-PCR was performed to measure HIF-1α mRNA and Slug mRNA expressions in RA FLS under

hypoxia. RA FLS was transfected with HIF-1α cDNA to investigate the effect of overexpression of HIF-α on Slug

expression. Immunohistochemistry was used to assess the presence HIF-1α and Slug in RA synovial tissue. Microarray

analysis was performed to investigate the change in Slug gene expression when FLS were exposed to hypoxia. Finally, the

effect of TNF-α on Slug and HIF-1α expressions under normoxic conditions was assessed in RA FLS by Western blot.

Results: Hypoxia induced the expression of HIF-1α and phosphorylation of STAT3, but not JNK and ERK in RA FLS.

Pre-treatment of RA FLS with WP1066 inhibited the expression of p-STAT and HIF-1α under hypoxia. Hypoxic con-

ditions induced Slug mRNA expression, and overexpression of HIF-1α in RA FLS reproduced enhanced Slug expression.

Microarray analysis revealed a significantly up-regulated Slug expression. Immunohistochemical staining showed that

HIF-1 α and Slug were co-localized in the lining area of RA synovium. Stimulation of FLS with TNF-α alone without hy-

poxia resulted in increased expression of HIF-1α and Slug.

Conclusion: Our study demonstrates that HIF-1α expression from RA FLS induced by hypoxia or TNF-α alone is

mediated through JAK/STAT3 signaling pathway, which ultimately leads to the expression of Slug.

Poster 9


S188

Pioneering Study about Expression of Programmed Death-1 (PD-1) with Its Ligands on Synoviocyte, Macrophage and

Lymhpocyte in Synovial Fluid of Rheumatoid Arthritis

Sang Yeob Lee1, Sung Won Lee1, Won Tae Chung1, Jae Ho Bae2

1Department of Rheumatology. Division of Internal Medicine. Dong-A Uiversity, Busan, 2Biochemistry, Pusan National University, Yong -San, Korea

Introduction: Programmed death 1 (PD-1) plays a key role in the negative regulation of the immune response and plays

a key role in the induction of immune tolerance in the cancer microenvironment. PD-1 ligand expressing cancer cells

evaded from PD-1 expressed antigen-specific T cells. In this study, we investigated the expression of PD-1 and PD-1 li-

gand on synoviocyte, macrophage and lymphocyte in RA synovial fluid.

Methods: Eight RA patients were enrolled. They were high disease activity {mean DAS (CRP)=3.8}. RA synoviocyte,

macrophage and monocyte cultured from the synovial fluid of the knee joint of each subject, were used for experiments.

Percentage of PD-1+ and PD-1 + ligand cells were measured by flow cytometry.

Results: PD-1 expression was significantly increased synoviocyte, macrophage and lymphocyte in RA (p=0.002 and

p<0.001, respectively) Similarly, PD-1 Ligand was also upregulated in synoviocyte, macrophage and lymphocyte in RA.

Conclusion: PD-1 and PD-1 ligand were expressed in RA synoviocytes, macrophage and monocyte. These dates sug-

gested that RA was very complex immune disease and the role of PD-1 and PD-1 ligands in PA were needed more

experiments.

Poster 10


S189

The Jak-2 Mutation in Rheumatoid Arthritis Pathogenesis

Taskin Senturk1, Ikbal Akdam1, Irfan Yavasoglu2, Gohan Bozkurt3

Departments of 1Rheumatology, 2Hematology and 3Genetics, Adnan Menderes University, Aydin, Turkey

Background: The Janus kinases, Jaks, constitutively associate with the cytoplasmic region of cytokine receptors and

play an important role in a multitude of biological processes. The JAK2 gene provides instructions for making a protein

that promotes the growth and division (proliferation) of cells. This protein is an important intracellular mediator of cyto-

kine signaling by JAK/STAT pathway and mutations has been implicated in myeloproliferative diseases and leukemia.

Aberrant JAK activity is also associated with immune diseases such as rheumatoid arthritis (RA). We aim to investigate

relationship between Jak-2 V617F mutation and pathogenesis of rheumatoid arthritis.

Objective: To investigate Jak-2 V617F mutation in patients with RA.

Method: Diagnosed by 2010 ACR/EULAR classification criteria of 27 seropositive, 22 seronegative RA patients and

22 healthy controls were included in this study. Jak-2 V617F mutations studied Real-time quantitative PCR methods in

all groups. DNA was isolated from 200μL whole blood.

Results: In healthy controls, only one heterozygous Jak-2 V617F mutation detected (%0.04), but in all RA patients het-

erozygous or homozygous mutations not detected (%0.00).

Conclusion: We concluded that there was no relationship between RA and JAK-2 V617 mutation. The hematopoietin

family of cytokines, which includes several postulated to have roles in RA (e.g., interferons, IL-6, IL-2, IL-7, IL-12, IL-15)

bind to Type I and II cytokine receptors and signal through the janus kinase-signal transducers and activators of tran-

scription (Jak-STAT) pathway. Otherwise, JAK have been identified like as Jak1,Jak2, Tyk2, and Jak3. Accordingly, all gene

mutations of JAK should be investigated for pathogenesis of rheumatoid arthritis.

Poster 11


S190

Identification of Differential Expressions of NOD-like Receptors and Their Signaling Pathway

in Rheumatoid FLS and Synovium

Ji-Yoen Moon1, Byung Wook Park2, Yong-Jin Kwon1, Hye Won Kim1, Min-Chan Park1

1Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, 2Chadwick International School, Songdo, Incheon, Korea

Objectives: This study was performed to investigate the differential gene expressions and protein productions of nu-

cleotide oligomerization domain (NOD)-like receptors (NLRs) in RA and to identify their dominant signaling pathways.

Methods: Gene expressions and protein productions of proinflammatory NLRs, including NLRP1, NLRP3, NLRC1,

and NLRC2, and anti-inflammatory NLRs, including NLRP12, NLRX1, and NLRC3, were determined in FLS and syno-

vium from patients with RA or OA using real-time quantitative RT-PCR, immunohistochemistry and Western blot

analysis. The effects of their gene regulations on inflammatory gene expressions and caspase-1 were assessed using real

time PCR and on TRAF6, NF-κB, and IKK productions were analyzed using Western blot analysis after RNAi plasmid

or E.coli vector encoding NLRs treatments.

Results: Gene expressions and protein productions of NLRP1, NLRP3, NLRC1, NLRP12, and NLRC3 did not show any

differences between RA and OA samples. Expression and production of NLRC2 were increased, and those of NLRX1

were decreased in RA, compared to those from OA samples. Proinflammatory gene expressions of TNF-α, IL-1β, IL-6,

and COX-2 were increased in NLRC2 RNAi plasmid-transfected RA FLS, and transfection with E.coli vectors encoding

NLRX1 induced reductions in those levels. The expressions of caspase-1 were increased by NLRC2 RNAi plasmids treat-

ment and were decreased by adenoviral vectors encoding NLRX1. Regulations of NLRC2 and NLRX1 gene expression

did not alter TRAF6, NF-κB, and IKK levels.

Conclusion: We found that proinflammatory NLRC2 is increased and anti-inflammatory NLRX1 is decreased in RA

FLS and synovium and that their main action mechanisms are mediated by caspase-1, rather than NF-κB signaling

pathways. To our knowledge, this study is the first to show the presence and differential expressions of NLRs in RA syno-

vial tissues and can our data suggest that NLRs might be involved in pathogenesis of RA.

Poster 12


S191

Histamine and Histamine H4 Receptor Promotes Osteoclastogenesis in Rheumatoid Arthritis

Hae-Rim Kim1, Kyung-Ann Lee1, Kyoung-Woon Kim2, Bo-Mi Kim1,2, Sang-Heon Lee1

1Department of Rheumatology, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, 2Concersant Research Consortium in Immunologic Disease, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea

Objective: The biological function of histamine is mediated through four types of histamine H1~H4 receptors.

Histamine H4 receptor (H4R) has immune-modulatory and chemotaxic effects and various immune cells express H4R.

This study aimed to determine the osteoclastogenic role of H4R in rheumatoid arthritis (RA).

Methods: The expression of H4R in RA synovial fluid mononuclear cells (SFMCs), synovial fibroblasts and peripheral

blood mononuclear cells (PBMCs) using real-time polymerase chain reaction (PCR). After RA SFMCs and PBMCs were

treated with histamine, Th17 cytokines, such as IL-17, IL-21 and IL-22, and H4R antagonist (JNJ7777120), the gene ex-

pression and protein production of H4R and RANKL were determined by real-time PCR and ELISA. Osteoclastogenesis

was assessed by counting tartrate-resistant acid phosphatase-positive multinucleated cells in peripheral blood CD14+

monocytes cultured with histamine, Th17 cytokines and JNJ7777120.

Results: The synovial fluid and serum concentration of histamine was higher in RA, compared with osteoarthritis and

healthy controls, respectively. The expression of H4R was increased in RA PBMCs compared with healthy controls.

Histamine, IL-17, IL-21 and IL-22 stimulated the expression of H4R and RANKL in PBMCs and JNJ7777120 reduced the

histamine and Th17 cytokine-induced RANKL expression. Histamine and Th17 cytokines also induced the osteoclast dif-

ferentiation from peripheral blood monocytes and JNJ7777120 decreased the osteoclastogenesis.

Conclusion: H4R mediates RANKL expression and osteoclast differentiation induced by histamine and Th17

cytokines. The blockage of H4R could be a new therapeutic modality for prevention of bone destruction in RA.

Poster 13


S192

Rheumatoid Arthritis is Associated with Low/mid Frequency Hearing Impairment: Results from the 2010-2012 Korean

National Health and Nutrition Examination Survey

Hyemin Jeong1, Young-Soo Chang2, Sun Young Baek3, Sun Woo Kim3, Yeong Hee Eun1, In Young Kim1, Jaejoon Lee1, Eun-Mi Koh1, Hoon-Suk Cha1

1Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 2Department of otorhinolaryngology, The Armed Forces Daejeon Hospital, Daejeon, 3Biostatic and Clinical Epidemiology Center, Samsung Medical Center, Seoul, Korea

Introduction: To evaluate the association between rheumatoid arthritis (RA) and hearing impairment in the Korean

adult population.

Method: Audiometric and laboratory test data from the 2010-2012 Korean National Health and Nutrition Examination

Survey (KNHANES) were used for analysis. Logistic regression were performed to adjust various possible factors asso-

ciated with hearing impairment. We defined hearing impairment for 2 categories of frequency (low/mid, high): Low/mid

frequency, average of 0.5, 1.0, and 2.0 kHz and high frequency, average of 3.0, 4.0, and 6.0 kHz.

Results: A total of 15,598 subjects completed the audiometric tests. The overall weighted (n=32,898,665) prevalence

of RA was 1.5%. Subjects with RA were older and showed lower education level and demonstrated high prevalence of

hypertension, diabetes, and chronic kidney disease than subjects without RA. Frequency of hearing impairment was

higher in subjects with RA than subjects without RA in both Low/mid and high frequency (22.0 vs 7.8%, p<0.001 and

43.3 vs. 26.4%, p<0.001, respectively). In multivariable logistic analysis, RA (OR 1.54, 95% CI 1.07 to 2.22, p=0.021)

was independent risk factor for low/mid frequency hearing impairment along with age (OR 1.12, 95% CI 1.11 to1.13,

p<0.001), college graduation (OR 0.51, 95% CI 0.38 to 0.69, p<0.001), and occupational exposure (OR 1.46, 95% CI

1.19 to 1.81, p<0.001). In the analysis of high frequency hearing impairment, RA did not show any association with hear-

ing impairment.

Conclusion: This study first demonstrated that RA was associated with the low/mid frequency hearing impairment af-

ter adjustment with various known risk factors.

Poster 14


S193

High Fat Mass Predicts the Persistence/Progression of Musculoskeletal Pain in Community Residents

Hyun-Ah Kim1, Seung Hun Lim2, Nam Han Cho3

1Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, 2Department in Preventive Medicine, Ajou University School of Medicine, Suwon, Korea

Objective: Previously we reported that fat mass, muscle mass, and fat/muscle mass ratio as well as body mass index

(BMI), and musculoskeletal (MS) pain was significantly correlated (JJ Yoo et al. AR, 2014). The objective of the present

study was to evaluate the influence of BMI, fat mass, muscle mass, and fat/muscle mass ratio on the persistence and pro-

gression of MS pain after 3 years in community residents.

Methods: In the Korean Health and Genome Study, 1325 participants completed pain questionnaire and underwent

dual x-ray absorptiometry calculating body composition in year 2007 and 2010. Widespread pain was defined as pain

above the waist, below the waist, on both sides of the body and in the axial region. Three other categories of pain in these

analyses were pain in two or more regions that did not meet the criteria for widespread pain, pain in one region, and no

pain. After 3 years of follow-up, subjects were categorized into non-progressor and persistence/progressor. Tests for a lin-

ear trend across categories of pain constellations were performed using Mantel-Haenszel chi-square tests for categorical

variables and the F-statistics from linear regression models for continuous variables.

Result: Among persistence/progressor, the proportion of females was significantly higher and the mean age was sig-

nificantly older. BMI, fat mass, and fat mass/muscle mass ratio was significantly higher among persistence/progressor.

After multivariate logistic regression analysis, female gender, obesity and self-reported hand and knee arthritis were sig-

nificantly associated with persistence/progression of MS pain. Fat mass and fat/muscle mass ratio was significantly cor-

related with persistence/progression of MS pain only among female. The prevalence of metabolic syndrome did not affect

persistence/progression of MS pain in either normal or high BMI group.

Conclusion: High Fat mass, and fat/muscle mass ratio predicts the persistence/progression of MS pain in female

subjects.

Poster 15


S194

Biological Function Enriched Prediction of Severe Radiographic Progression in Rheumatoid Arthritis

Young Bin Joo1, Yul Kim2, Youngho Park3, Kwangwoo Kim3, Jeong Ah Ryu4, Seunghun Lee4, So-Young Bang3, Hye-Soon Lee3, Gwan-Su Yi2, Sang-Cheol Bae3

1Department of Rheumatology, St Vincent's Hospital, The Catholic University of Korea, 2Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, 3Department of Rheumatology,

Hanyang University Hospital for Rheumatic Diseases, 4Department of Radiology, Hanyang University Hospital

Background: Although radiographic damage in rheumatoid arthritis (RA) is highly heritable, genetic information is

still lack for prediction of radiographic damage. More reliable prediction could be established from biological function en-

riched analysis.

Objectives: To find out a biological relevant set of single nucleotide polymorphisms (SNPs) for prediction of radio-

graphic progression in RA patients using genome-wide association study (GWAS) combined with bioinformatics

analysis.

Methods: We obtained genome-wide SNP data for 374 RA patients using Illumina HumanOmni2.5Exome-8 arrays.

Significant SNPs for radiographic progression from GWAS were mapped on the functional genes and re-ranked in order

of higher RA correlation scores. Based on this post-GWAS analysis, an optimal set of SNPs for prediction of radiographic

progression was selected using support vector machine (SVM). Prediction accuracy of our model was compared with oth-

er models obtained by GWAS and SPOT, one of the post-GWAS analyses, using wilcoxon signed-rank test. Pathway en-

richment analysis was done using DAVID.

Results: A total, 36,091 significant SNPs with p-value<0.05 from GWAS were reprioritized using post-GWAS analysis.

In 10-fold cross-validation using SVM classifier, the best average accuracy was 0.6342 with 120 SNPs and increased to

0.7565 as combined with clinical information. As compared the prediction accuracy of our model with GWAS or SPOT,

0.7827 of AUC in our model was superior to those obtained by GWAS (AUC 0.5969, p-value 0.0019) and SPOT (AUC

0.6737, p-value 0.0371). Top-ranked 120 SNPs associated with radiographic progression in post-GWAS analysis were en-

riched in cytokine-cytokine receptor interaction, pathways in cancer, Jak-STAT signaling pathway, and chronic myeloid

leukemia (all FDR<0.05).

Conclusion: We identified an optimal set of SNPs to predict radiographic progression in patients with early RA, which

showed outstanding prediction accuracy than GWAS or other post-GWAS.

Poster 16


S195

A Korean Multicenter Observational Study of Disease Activity Changes in BIologic versus Non-biologic Users with

Seropositive Rheumatoid Arthritis

Kichul Shin1, Sung Soo Kim2, Sang Heon Lee3, Seung Jae Hong4, Sung Jae Choi5, Jung yoon Choe6, Seung- Geun Lee7, Hoon-Suk Cha8, Eun Young Lee9, Sung-Hwan Park10, Jin Wuk Hur11, Sung Soo Na12,

Chang Hee Suh13, So Min Wook14, Seung Won Choi15, Dong Hyuk Sheen16, Won Park17, Shin-Seok Lee18, Myong Joo Hong19, Jin Seok Kim20, Jung Soo Song21, Hye Soon Lee22, Seong Ho Kim23, Dae-Hyun Yoo24

1Division of Rheumatology, SMG-SNU Boramae Medical Center, Division of Rheumatology, 2Gangreung Asan Hospital, 3Division of Rheumatology, Konkuk University Medical Center, 4Division of Rheumatology, KyungHee University Hospital, 5Division of Rheumatology, Korea University Ansan Hospital, 6Division of Rheumatology, Daegu Catholic University Medical Center, 7Division of Rheumatology, Pusan National University Hospital, 8Division of Rheumatology, Samsung Medical Center, 9Division of Rheumatology, Seoul National University Hospital, 10Division of Rheumatology, Catholic University of Korea, Seoul St. Mary's Hospital, 11Division of Rheumatology, Eulji Generall

Hospital, 12Division of Rheumatology, Soonchunghyang University Cheonan Hospital, 13Division of Rheumatology, Ajou University Hospital, 14Division of Rheumatology, Pusan National University Yangsan Hospital, 15Division of Rheumatology, Ulsan University Hospital, 16Division of Rheumatology, Deajun Eulji University Hospital, 17Division of Rheumatology, Inha University Hospital, 18Division of Rheumatology, Chonnam National University Hospital, 19Division of Rheumatology, Chonbuk National University Hospital, 20Division of Rheumatology, Jeju National

University Hospital, 21Division of Rheumatology, Chung-Ang University Hospital, 22Division of Rheumatology, Hanyang University Guri Hospital, 23Division of Rheumatology, Inje University Haeundae Paik Hospital, 24Division of Rheumatology, Hanyang University Hospital

Background: Biologic disease modifying anti-rheumatic drugs (DMARDs) have become an important arsenal for rheu-

matoid arthritis (RA) treatment. However, studies comparing outcomes of biologic (b) DMARD versus non-biologic

(nb) DMARD use in Korean RA patients are limited to date.

Objective: To follow the changes of the simplified disease activity index (SDAI) of seropositive RA patients in daily clin-

ical practice.

Methods: KOSDAI is a multicenter observational study that was launched in Jan 2012 in 24 secondary or tertiary cen-

ters nationwide. Seropositive patients who met the 2010 ACR/EULAR classification criteria for RA, and had ³ 3 tender

and ³ 2 swollen joints, and abnormal inflammatory markers were enrolled consecutively. Disease activity including SDAI,

laboratory findings and patient reported outcomes were obtained at baseline, 6 months, and 12 months. Serial SDAI

changes and the 2011 ACR/EULAR clinical remission rate at 12 months were assessed.

Results: Eight hundred and fifty patients participated in this study. The retention rate of DMARDs at 12 months was

82.3%. Mean SDAI score at baseline was higher in the bDMARD group than the nb DMARD group (32.08±12.98 vs

25.69±10.97, p<0.0001). The reduction of the SDAI score was significant (12 months-baseline) in both groups; mean

SDAI reduction -19.0 in the bDMARD group, -12.6 in the nbDMARD group. Patient’s global assessment, Korean HAQ

at 12 months also improved accordingly in both groups. Clinical remission rate in the bDMARD an nbDMARD group at

12 months were 15.4%, 14.6%, respectively. A multivariate logistic regression model showed that baseline KHAQ score

was the most notable factor determining remission in this study.

Conclusion: The KOSDAI study indicates that Korean Rheumatologists are succesfully treating RA patients with prop-

er selection of DMARDs. Attaining higher clinical remission rates is an essential, reachable objective in our daily practice.

Poster 17


S196

Seropositivity and Its Impact on Radiographic Damage in Korean Rheumatoid Arthritis Patients Starting Biologics

Kichul Shin1, Seungjun Ha1, Inkyung Jung2, Hyoun-Ah Kim3, Shin-Seok Lee4

1Division of Rheumatology, Department of Internal Medicine, SMG-SNU Boramae Medical Center, 2Department of Biostatistics, Yonsei University College of Medicine, 3Department of Rheumatology, Ajou University School of Medicine,

4Department of Rheumatology, Chonnam University Medical School

Background: High titers of rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACCP) are poor

prognostic factors for rheumatoid arthritis (RA) patients. Only few studies have investigated the clinical subtypes based

on seropositivity; double (RF/ACCP), RF or ACCP positive (+), double negative (-ve) (seronegative, SN) and its impact

on RA disease status.

Objective: To analyze the demographic and clinical data in active RA patients based on seropositivity.

Method: Patients were selected from the Korean College of Rheumatology Biologics Registry (KOBIO), a nationwide

inception cohort operating since 2013. Data regarding demographics, comorbidity, disease activity, medication, imaging

and laboratory tests were analyzed by a biostatistician (HS). After adjusting for gender, age, and disease duration, odd

ratio (OR, with 95% confidence interval [95% CI]) of RF, ACCP was calculated for predicting prevalent erosions at

baseline.

Results: Total 1198 RA patients who were to start a biologics was analyzed. Mean age was 57.2 years, and mean disease

duration was 8.3 years. Mean DAS28-CRP was 4.99, and erosion in hands or feet were found in 40.1% of patients.

ACCP+ was associated with prevalent erosions (OR 1.69 [95% CI 1.13-2.52] p=0.0096), better than RF+ (OR 1.03

p=0.83) but no superior than RF/ACCP (OR 2.19 [95% CI 1.19-4.01] p=0.012). Of note, ACCP+ only (RF-ve) was

strongly associated with presence of erosions (OR 4.93 [95% CI 2.29-10.61], p<0.0001) in our analysis. Other baseline

clinical characteristics were comparable between RF/ACCP, RF+, ACCP+, and the SN group at the time point of starting

biologics, yet C-reactive protein was significantly higher in the SN group.

Conclusion: Our data corroborate the significance of ACCP+ in predicting radiographic damage in active RA patients.

In particular, the subgroup of ACCP+/RF-ve active RA patients would need further attention to achieve early disease

control.

Poster 18


S197

Achievement of Imaging Remission among Patients with Rheumatoid Arthritis in Clinical Remission

and Their Characteristics
















flammatory drug (NSAID) (n=15 vs 19 patients, p=0.019). Overall, imaging remission was related with less tender and

swollen joint count, lower patient global assessment score, higher health assessment questionnaire (HAQ) score and

lower clinical disease activity score.

Conclusion: Achievement rate of imaging remission was 54.3% in RA patients with clinical remission. Patients who

were in imaging remission tend to have lower disease activity, lower pain score and less frequent use of NSAIDs, com-

pared to patients with only clinical remission.

Poster 19

Withdraw


S198

Achievement of Imaging Remission among Patients with Rheumatoid Arthritis in Clinical Remission

and Their Characteristics
















flammatory drug (NSAID) (n=15 vs 19 patients, p=0.019). Overall, imaging remission was related with less tender and

swollen joint count, lower patient global assessment score, higher health assessment questionnaire (HAQ) score and

lower clinical disease activity score.

Conclusion: Achievement rate of imaging remission was 54.3% in RA patients with clinical remission. Patients who

were in imaging remission tend to have lower disease activity, lower pain score and less frequent use of NSAIDs, com-

pared to patients with only clinical remission.

Poster 20

Withdraw


S199

Assessment of Liver Fibrosis Using Transient Elastography in Patients with Rheumatoid Arthritis

Exposed to Long Term Methotrexate

Min Kyung Chung, Jung Hee Koh, Jennifer Lee, Seung-Ki Kwok, Ji Hyeon Ju, Sung-Hwan Park

Division of Rheumatology, Department of Internal medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea

Background: Methotrexate (MTX) has been recommended for the first line therapy of rheumatoid arthritis (RA), ei-

ther alone or in combination with other DMARDs such as leflunomide. Although MTX is thought to have long term safe-

ty, there is still controversy whether long term use of MTX and its cumulative dose causes liver fibrosis (LF) in RA

patients.

Objectives: This study was performed to assess the degree of LF among the RA patients treated with MTX by transient

elastography (TE), and to identify associated factors with LF in those patients.

Methods: We restrospectively reviewed the medical records of 160 patients with RA taking MTX over 3 years, and who

had LF examination using TE. LF was defined as liver stiffness value over 5.3 kPa. The duration, cumulative doses of med-

ications including MTX and leflunomide, and serologic markers related to LF were analyzed by comparing 2 groups with

and without LF.

Results: The mean disease duration of patients was 10.7±5.1 years, and the median liver stiffness value was 4.5±2.7

kPa. Twenty one (13.1%) patients showed LF while only 1 (0.01%) patient progressed to liver cirrhosis. The cumulative

dose of MTX and leflunomide showed no significant difference between 2 groups. A history of taking LFNM and con-

comitant medications did not affect to the development of LF. Patients with LF had higher glucose, aspirate amino-

transferase (AST), and alkaline phosphate (ALP) level with a tendency of longer treatment duration with MTX. The dura-

tion of MTX (odds ratio [OR] 1.245, P=0.011), serum glucose level (OR 6.089, P=0.022), and AST level (OR 1.054,

P=0.015) were related with LF in multivariate analysis.

Conclusion: Long term use of low dose MTX and combination of leflunomide in patients with RA were relatively safe

in terms of severe LF measured by TE. RA patients with risk factors such as impaired glucose tolerance should be more

carefully monitored for development of LF in long term use of MTX.

Poster 21


S200

The Effect of TNF Blockers on Bone Mineral Density in Rheumatoid Arthritis Patients Receiving Bisphosphonate

Doo-Ho Lim1, Byeongzu Ghang2, Seokchan Hong2, Yong-Gil Kim2, Chang-Keun Lee2, Bin Yoo2

1Division of Rheumatology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, 2Division of Rheumatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Background: Osteoporosis is more frequently observed in patients with rheumatoid arthritis (RA) than in general

population. Bisphosphonate (BP), which suppresses bone resorption by inhibiting osteoclast activation, has been most

commonly used for treatment of osteoporosis. Previous studies demonstrated that anti-TNF therapy has a beneficial ef-

fect on bone loss possibly through anti-inflammatory effects as well as its inhibitory effects on osteoclast activation.

However, there have been few studies assessing the role of TNF blocker for osteoporosis in RA patients under con-

comitant treatment with BP.

Objectives: We performed a retrospective longitudinal study to investigate the changes in bone loss in RA patients re-

ceived BP with or without TNF blockers.

Methods: One hundred and seven RA patients who were diagnosed with osteoporosis and treated with BP between

Jan. 2005 and Dec. 2013, were reviewed retrospectively. Bone mineral density (BMD) (g/cm2) of the lumbar spine, femur

neck, trochanter and total femur was measured by dual-energy X-ray absorptiometry. Last follow-up BMD was obtained

at 4.62±2.9 years after initial acquisition of BMD. The rate of change in the BMD was expressed as the annualized per-

centage change of BMD between initial measurement and subsequent measurement.

Results: Among RA patients receiving BP with (n=19) and without TNF blockers (n=88), 19 (100.0%) and 80

(90.9%) were women, respectively. The mean ages at initial BMD for these subjects were 67.4±10.3 years and 66.1±8.3

years, respectively (p=0.569). The annualized changes of BMD in femur neck was significantly different between RA pa-

tients receiving BP with or without TNF blockers (1.25±6.0 vs. -0.72±3.0 %/year, respectively [p=0.038]), while there

were no differences in other sites.

Conclusion: In RA patients with osteoporosis even receiving BP, TNF blockers might have additional benefit for bone

loss in femur neck, possibly lowering hip fracture.

Poster 22


S201

A Rare Case of Branch Retinal Vein Occlusion Complicating Rheumatoid Arthritis

Mi-Hye Kwon1, Younghoon Lee2, Chung-Il Joung1

Departments of 1Internal Medicine, 2Ophthalmology, Konyang University College of Medicine, Daejeon, Korea

Branch retinal vein occlusion (BRVO) is an ophthalmic disease that the distal retinal venous system is occluded by con-

ditions such as thrombosis. Patients with BRVO may be asymptomatic, or experience decreased vision depending on the

location, extent of lesion and complications such as macular edema or vitreous hemorrhage. Risk factors for developing

retinal vein occlusion (RVO) are HTN, DM, smoking, obesity, and hypercoagulable state. In rheumatic disorders,

Behçet’s disease, lupus, and antiphospholipid syndrome have been reported as complicated by retinal vessel diseases in-

cluding RVO. While, rheumatoid arthritis (RA) is hardly associated with RVO, rather more with keratoconjunctivitis sic-

ca, episcleritis or scleritis. We report a RA patient complicated by BRVO treated with intravitreal bevacizumab.

A 65-year-old woman presented with painful swelling of metatarsophalangeal joints for a few weeks and was diag-

nosed as having seropositive RA in May 2013. She was prescribed with methotrexate, then sulfasalazine was added for

increased activity of RA in Oct 2014, and celecoxib was intermittently prescribed for joint pain. RA disease activity had

been minimal thereafter, suddenly she developed decreased vision in the left eye and visited department of ophthalmol-

ogy and was diagnosed as BRVO in the supratemporal vein with hemorrhage (Fig. 1A) and macular edema (Fig. 1B).

Ophthalmologist performed intravitreal injection of bevacizumab, an off-label treatment for anti-VEGF. Her vision has

improved gradually and hemorrhage completely absorbed (Fig. 2A) although mild cystic macular edema sustained (Fig.

2B). We searched for known risk factors for BRVO in this patient but she did not have HTN, DM, obesity, smoking history,

hypercoagulable state, nor another rheumatic disease. We experienced a rare case of BRVO in a RA patient, and report

it here.

Fig. 1.

Fig. 2.

Poster 23


S202

On Drug and Drug-Free Remission by Baseline Disease Duration: Abatacept Versus Methotrexate Comparison

in Patients with Early Rheumatoid Arthritis

Vivian P. Bykerk1, Gerd R. Burmester2, Bernard G. Combe3, Daniel E. Furst4, Tom W.J. Huizinga5, Dennis A. Wong6, Paul Emery7

1Department of Rheumatology, Weill Cornell Medical College-Cornell University, United States, 2Department of Rheumatology, Charité - University Medicine Berlin, 3Department of Rheumatology, Montpellier-Nimes University, France, 4Division of Rheumatology,

University of California Los Angeles, United States, 5Department of Rheumatology, Leiden University Medical Center, Netherlands, 6Bristol-Myers Squibb, United States, 7Department of Rheumatology, University of Leeds, United Kingdom

Background: Patients with RA and longer disease duration generally do not respond as well to treatment with

DMARDs as patients with a shorter disease duration. Earlier use of biologic (b) DMARDs can improve disease control.

Objectives: This AVERT trial post-hoc analysis examines outcomes in patients with varying degrees of early disease

duration in which the definition for disease duration is well defined across groups.

Methods: Patients with early active RA (persistent symptoms for ≤2 years and DAS28 [CRP] ≥3.2), and who were an-

ti-CCP2 positive, were randomized to SC abatacept (ABA) + MTX, SC ABA alone or MTX alone for 12 months. All RA

treatment was removed after 12 months in patients with DAS28<3.2. In this post hoc analysis, proportions of patients

achieving protocol-defined remission (DAS28<2.6) were assessed by ≤3 months', >3 to ≤6 months' or >6 months' dis-

ease duration (defined as the duration of persistent symptoms at baseline) and treatment group.

Results: Patients were randomized and treated with ABA+MTX (n=119) or MTX (n=116): 36 and 48 with ≤3

months'; 34 and 29 with >3 to ≤6 months'; 49 and 39 with >6 months' disease duration, respectively. No systematic dif-

ferences were seen in baseline demographics and clinical characteristics for patients grouped by disease duration.

Irrespective of baseline disease duration, a higher proportion of ABA+MTX-treated patients achieved Month 12 and sus-

tained (Month 18) remission, compared with MTX alone. A higher proportion of ABA+MTX-treated patients with dis-

ease duration ≤3 months maintained remission following all treatment withdrawal compared with longer disease dura-

tions and MTX alone. ABA+MTX-treated patients with ≤3 months' disease duration also had the fastest onset of re-

sponse (Fig. 1).

Conclusion: Disease duration of ≤3 months was associated with faster onset of clinical response and the ability to ach-

ieve higher rates of drug-free remission following treatment with ABA+MTX in AVERT.

Poster 24


S203

Abatacept Plus Methotrexate Can Effectively and Safely Regain the Target of Remission Following

Re-treatment for Flares after Drug-Free Withdrawal in Patients with Early Rheumatoid Arthritis

Paul Emery1, Gerd R. Burmester2, Vivian P. Bykerk3, Bernard G. Combe4, Daniel E. Furst5, Michael Maldonado6, Thomas W. Huizinga7

1University of Leeds, United Kingdom, 2Charité - University Medicine Berlin, Germany, 3Department of Rheumatology, Hospital for Special Surgery, Weill Cornell Medical College, New York, New York, USA, 4Department of Rheumatology, Service d’ Immuno-Rheumatologie,

Montpellier, France, 5Department of Medicine, University of California Los Angeles, Los Angeles, USA, 6Bristol-Myers Squibb, New Jersey, Princeton, USA, 7Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands

Background: AVERT was a Phase IIIb, randomized, active controlled study to evaluate efficacy and safety of abata-

cept(ABA) over three treatment phases: treatment, following therapy withdrawal, and re-exposure.

Objective: Assess treatment outcomes during treatment withdrawal and re-exposure periods.

Methods: MTX-naïve, anti-CCP-positive pts with early RA (onset of symptoms ≤2 yrs) were initially randomized to

12 months of weekly SC ABA+MTX, ABA mono or MTX alone (treatment period). Pts with DAS28 (CRP)<3.2 at Month

12 then entered a 12 month withdrawal period with no treatment. All pts with protocol-defined flare after Month 15

could receive open-label ABA+MTX (re-exposure period) for 6 months.

Results: Most pts could not remain treatment-free after complete withdrawal, due to worsening disease activity

(172/225; 76.4%) during the 12 month withdrawal period. Of those who entered withdrawal, rates of pts maintaining

DAS28<2.6 free of drugs at 24 months were 14.0, 12.3 and 11.3% for ABA+MTX, ABA mono and MTX alone,

respectively. A total of 146 pts entered the re-exposure period and 140 completed. The mean (SD) DAS28 at re-exposure

period entry was 5.47 (1.27) and at the end of the re-exposure period was 2.43 (0.95). A total of 62% (78/126) of evalu-

able pts were in DAS28 remission on Day 169 of re-exposure period. Over the 12 months withdrawal period, the num-

bers(%) of serious AEs were 2 (2.4), 0 (0) and 5 (6.7), respectively. In the re-exposure period, no pts discontinued due

to AEs and no serious infections were reported (292.2 pt-yrs). The overall infection rates were 8.9 and 16 (incidence

rate/100 pt-yrs) in the withdrawal and re-exposure periods, respectively.

Conclusion: Re-treatment with ABA+MTX can effectively recapture prior remission following flare after complete

therapy withdrawal. There were fewer infection events in the combined withdrawal and re-exposure and only 1 serious

infection during withdrawal and treatment period, suggesting re-treatment is well tolerated.

Poster 25


S204

Factors Associated with Hydroxychroloquine Retinal Toxicity

Ji-Won Kim1, Chan Uk Lee1, Ji-Na Kim1, Se Eun Kim2, Yun Young Kim2, Hwajeong Lee1, Sung-Hoon Park1, Seong-Kyu Kim1, Jung-Yoon Choe1

1Division of Rheumatology, Department of Internal Medicine, 2Ophthalmology, Catholic University of Daegu School of Medicine, Daegu, Korea

Background: Hydroxychloroquine (HCQ) is widely used drug in autoimmune diseases, and is known to cause retinal

toxicity. Since several studies investigated risk factors for HCQ retinal toxicity, there were limited data in Korea.

Objective: This study was designed to investigate factors which increase the risk of HCQ retinal toxicity in Korean

patients.

Methods: Twenty-seven patients of rheumatoid arthritis or systemic lupus erythematosus, who were using or had used

HCQ, were enrolled in our study and sent to an ophthalmologist. Several tools including spectral domain optical coher-

ence tomography, fundus autofluorescence, and visual field test were used to screen retinal toxicity. Retrospective chart

review of all patients was done. Logistic regression analysis was performed to identify factors associated with HCQ reti-

nal toxicity.

Results: We identified 4 patients (14.8%) of HCQ retinal toxicity among 27 patients. Of the 4 patients with retinal tox-

icity, 2 patients had pericentral pattern of retinal toxicity and the other 2 patients had mixed pattern of retinal toxicity.

Total HCQ dose (odds ratio 1.40, 95% Cl 1.03-1.89 for Total HCQ dose in 100-g increments) and duration of HCQ use

(odds ratio 1.60, 95% Cl 1.05-2.43 for HCQ duration in 1-year increments) increased the risk of retinal toxicity.

Conclusion: HCQ retinal toxicity was associated with total HCQ dose and duration of HCQ use. In addition, further

investigation of other risk factors including genetic factor is needed.

Keywords: Hydroxychloroquine, Retina, Toxicity, Risk factors

Poster 26


S205

Improvement of Morning Stiffness in Korean Rheumatoid Arthritis Patients after Treatment with

a New Modified-release form of Prednisone

Kichul Shin1, Sung-Soo Kim2, Sung Jae Choi3, Geun-Tae Kim4, Sang-Hyon Kim5, Myeong Soo Lee6, Jin-Wuk Hur7, Yun Sung Kim8, Young Il Seo9, Seong-Su Nah10, Hyun-Sook Kim10, Eun Young Lee11, Seung-Jae Hong12

1Division of Rheumatology, SMG-SNU Boramae Medical Center, 2Division of Rheumatology, Gangneung Asan Hospital, University of Ulsan College of Medicine, 3Division of Rheumatology, Korea University College of Medicine, Korea University Ansan Hospital, 4Division of

Rheumatology, Kosin University College of Medicine, 5Division of Rheumatology, Keimyung University Dongsan Medical Center, 6Division of Rheumatology, Wonkwang University Hospital, 7Division of Rheumatology, Eulji University College of Medicine, 8Division of Rheumatology,

Chosun University College of Medicine, 9Division of Rheumatology, Hallym University College of Medicine, 10Division of Rheumatology, Soonchunhyang University College of Medicine, 11Division of Rheumatology, Department of Internal Medicine, Seoul National University

College of Medicine, 12Division of Rheumatology, Department of Internal Medicine, Kyunghee University College of Medicine

Background: The Circadian Administration of Prednisone in Rheumatoid Arthritis Study (CAPRA-1 and -2) provided

further insights that chronotherapy with modified-release prednisone (MR) can improve morning stiffness (MS) and

benefit patients with active rheumatoid arthritis (RA). Never has MS been the primary endpoint in a large-scale trial in

Korea.

Objective: To investigate changes in MS and safety after 12 weeks of MR in Korean RA patients.

Methods: The K-IMPROvE study was a 12 week single-arm, open-label, phase 4 study conducted in 13 centers

(ClinicalTrial.gov NCT02072200). Patients had 1) duration of MS ≥ 45 minutes and<6 hours, 2) DAS28-ESR ≥ 3.2 and

3) pain visual analog scale (VAS) ≥30/100 mm. Patients could switch from prednisolone to an equivalent dose of MR,

or start MR 10 mg daily at enrollment. Duration/severity of MS, pain VAS, Korean HAQ, EQ-5D, DAS28, and laboratory

tests were obtained. Primary endpoint was the % change in duration of MS (12 week-baseline) in the full analysis

population. A revised ‘Pre-screening’ of MS was adopted early after initiating the study.

Results: One hundred sixty-four patients were screened, and 145 patients were enrolled in this study. 46.7% of pa-

tients were on the 5 mg MR dosage on study completion. The mean changes of MS duration in all patients was -17%

(p<0.0995). Patients who undergone the pre-screening process resulted in -34% reduction of MS duration at 12 weeks

(n=85, p<0.002). Secondary endpoints including reduction of MS severity (-44%), pain VAS (-32%), DAS28 (-24%) and

improvement of HAQ (+18.5%), EQ-5D (+36%) were all statistically significant. Adverse events (AE) did not differ

from the known profile of low-dose oral corticosteroids.

Conclusion: This open-label study supports that MR can improve MS duration and severity, as well as other clinical

parameters in Korean RA patients. A standardized method for obtaining MS information (Korean) is warranted for future

studies.

Poster 27


S206

Withdrawal of Nonsteroidal Anti-inflammatory Drugs in Rheumatoid Arthritis Patients with Low Disease Activity

Dong Jin Go1,2, Kichul Shin3, Han Joo Baek4, Seong Wook Kang5, Young Mo Kang6, Jae Bum Jun7, Yun Jong Lee8, Sung Hwan Park9, Yeong Wook Song1,2

1Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Seoul, 2Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine, Medical Research

Institute, Seoul National University, Seoul, 3Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Borame Medical Center, Seoul, 4Division of Rheumatology, Department of Internal Medicine, Gachon University Gil Hospital, Incheon,

5Division of Rheumatology, Department of Internal Medicine, Chungnam National University Hospital, Daejeon, 6Division of Rheumatology, Department of Internal Medicine, Kyungpook National University Hospital, Daegu,

7Division of Rheumatology, Department of Internal Medicine, Hanyang University, Hospital for Rheumatic Disease, Seoul, 8Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam,

9Division of Rheumatology, Department of Internal Medicine, Catholic University of Korea, Seoul St Mary’s Hospital, Seoul, Korea

Background: Although nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in relieving joint pain in rheuma-

toid arthritis (RA) patients, long-term use of NSAIDs can cause adverse effects.

Objectives: To examine the patient-reported outcome (PRO) and its associated clinical factors in RA patients with low

disease activity (LDA) after discontinuing NSAIDs.

Methods: This study was a 16-week, multi-center prospective open-label trial. RA patients who achieved LDA

(28-joint Disease Activity Score [DAS28]<3.2) who were on NSAIDs for more than a month discontinued the NSAIDs.

Acetaminphen (AAP) was used as the rescue medication. Changes of DAS28 and PRO including pain visual analogue

scale (pain-VAS) and Routine Assessment of Patient Index Data 3 (RAPID-3) score were assessed. NSAID was restarted

when patient’s pain was intolerable with AAP. The endpoint was to analyze the group of patients who continued to with-

draw NSAID. Patients were further classified to have “sustained effectiveness” who met the following: 1) pain-VAS ≤30

mm at week16 or increase less than 25% from baseline and 2) RAPID-3 score ≤6 at week16 or increase less than 25%

from baseline.

Results: A total of 109 RA patients with LDA were enrolled in the study. At the end of the study, 89 (84.8%) patients

had remained without restarting NSAID. In these patients, there was a difference in pain-VAS between baseline and week

16 (P=0.010). However, changes in RAPID-3 and DAS28 were insignificant (P=0.128 for RAPID-3 and P=0.638 for

DAS28) Moreover, 66 patients ended up to show sustained effectiveness without restarting NSAID. After adjustments

of covariables, we found out joint swelling was the detrimental factor in NSAID withdrawal (odd ratio [OR] 0.150, 95%

confidence interval [CI] 0.034-0.666, P=0.013) and sustained effectiveness (OR 0.312, 95% CI 0.101-0.964, P=0.043).

Conclusion: NSAIDs can be

attempted to discontinue in

RA patients with LDA, espe-

cially in patients without joint

swelling.

Poster 28


S207

Varicella-zoster Virus Specific Cell-mediated Immunity is Decreased in Patients with

Rheumatoid Arthritis Receiving Varicella Vaccine

Jung-Hee Koh, Jennifer Lee, Seung-Ki Kwok, Ji Hyeon Ju, Wan-Uk Kim, Sung-Hwan Park

Division of Rheumatology, Department of Internal Medicine, St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Korea

Backgrounds: Response to varicella vaccine in rheumatoid arthritis (RA) patients is thought to be impaired due to the

immunological alterations generated by the disease and disease modifying anti-rheumatic drugs (DMARDs).

Objective: To evaluate humoral and cellular immunity against the live attenuated varicella vaccine in the patients with

RA.

Methods: We performed a prospective study of the varicella vaccine in 38 RA patients without biologic DMARDs and

a comparison of 19 patients with OA who had not taken DMARDs and oral glucocorticoids. Peripheral blood mono-

nuclear cells were collected before receiving varicella vaccine and after 12 weeks of vaccination and then analyzed using

VZV-specific interferon gamma (IFN-γ) enzyme-linked immunospot (ELISPOT) assay. The level of VZV IgG antibodies

was measured at the baseline and 12 weeks.

Results: No patients developed varicella zoster after vaccination during follow-up period (mean 13.8±2.5 months).

RA patients and controls in baseline and 12 weeks were similar in Levels of VZV IgG. However, RA patients showed less

baseline and follow-up Spot-forming cells (SFC) counts in the IFN-γ ELISPOT assay than controls did (2 and 11 in base-

line; P=0.046, 4.5 and 30 in 12 weeks; P=0.001, respectively). SFC counts increased from baseline after vaccination in

both RA patients and controls. The level of acute phase reactant and disease activity index 28 (DAS28) were similar in

baseline and 12 weeks after vaccination in patients with RA. Few participants reported mild adverse event (7%). Four pa-

tients with RA were experienced worsening of disease activity (median disease activity score 28 in 12 weeks, 3.2 [IQR,

2.9-3.6]).

Conclusions: Patients with RA significantly reduced VZV-specific cellular immunity, while humoral immunity is sim-

ilar after VZV vaccination. Although cellular immune response was not sufficient, vaccination seems to be effective in

the prevention of varicella zoster clinically, without major adverse event.

Poster 29


S208

Body Mass Index Does Not Influence the Efficacy of Abatacept in Patients with RA Who are Biologic-DMARD Naïve:

6-Month Results from a Real-World, International, Prospective Study

Rieke Alten1, Hubert G Nüßlein2, Mauro Galeazzi3, Hanns-Martin Lorenz4, Xavier Mariette5, Alain Cantagrel6, Melanie Chartier7, Guillaume Desachy8, Coralie Poncet9, Christine Rauch10, Manuela Le Bars10

1Schlosspark-Klinik University Medicine, Berlin, 2University of Erlangen-Nuremberg, Nuremberg, 3University of Siena, Siena, Italy, 4University Hospital of Heidelberg, Heidelberg, Germany, 5Université Paris-Sud, Paris, France, 6Purpan Hospital, Toulouse,

7Chiltern International, Neuilly, 8Excelya, Biostatistician Group, Paris, 9Docs International, Nanterre, 10Bristol-Myers Squibb, France

Background: In RA, obesity may negatively affect clinical response to anti-TNFs. In contrast, real-world data show aba-

tacept (ABA) efficacy and retention are unaffected by BMI in patients(pts) with prior bDMARD failure.

Objective: 6 months treatment response was assessed, according to BMI, in bDMARD-naïve pts in the ACTION study.

Methods: ACTION is a 2-year, international, prospective, observational study evaluating retention and effectiveness

of IV ABA in RA pts. In this 6-month analysis of bDMARD-naïve pts, baseline characteristics and clinical response were

compared by BMI subgroup: underweight/normal (<25 kg/m2), overweight (25-<30 kg/m2) and obese (≥30 kg/m2).

Time to ABA discontinuation was estimated using Kaplan-Meier survival analysis and compared using log-rank tests.

Results: BMI was reported in 643/672(96%) pts of which 41%, 35%, 24%, were underweight/normal, overweight and

obese, respectively. Higher baseline BMI was associated with more active disease (mean [95% CI], DAS28-CRP, 4.6 [4.5,

4.7], 4.8 [4.7, 5.0] and 5.1 [4.9, 5.2] for BMI<25, 25-<30 and ≥30 kg/m2, respectively) and more women (74, 66 and

81%), more metabolic disorders (22, 29 and 46%), fewer RF positive (77, 68 and 67%) and anti-CCP positive (71, 63 and

63%) pts (for BMI<25, 25-<30 and ≥30 kg/m2, respectively). Overall retention rates at 6 months (K-M analysis) did not

differ across groups(84, 89 and 87%, for BMI<25, 25<30 and ≥30 kg/m2, respectively; log-rank p=0.290); no significant

differences between groups were observed in discontinuation rates due to safety (log-rank p=0.683) or efficacy (log-rank

p=0.516). After adjustment for baseline characteristics, BMI was still not a discontinuation risk factor (BMI<25 kg/m2;

HR [95% CI] 0.46 [0.22, 0.99] and 0.69 [0.34, 1.41] for BMI 25-<30 and ≥30 kg/m2, respectively; FIGURE).

Conclusion: Unlike anti-TNFs, high BMI does not impact ABA clinical response in bDMARD-naïve RA. These results

are similar to real-world results in pts with prior bDMARD failure.

Poster 30


S209

Safety of Biologics in Patients with Rheumatoid Arthritis and Hepatitis C Virus Infection: A Multicenter Retrospective Study

Hyun Mi Kwon1†, Kichul Shin2, Shin-Seok Lee3, Won Tae Chung4, Jisoo Lee5, Sang-Heon Lee6, Seong-Wook Kang7, Chang Hee Suh8, Seung-Jae Hong9, Ran Song10, Jung-Yoon Choe11, Yeong Wook Song1

1Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, 2Division of Rheumatology, SMG-SNU Boramae Medical Center, 3Chonnam National University Hospital, 4Dong-A University Hospital, 5Ewha Womans University Mokdong Hospital,

6Konkuk University Hospital, 7Chungnam National University Hospital, 8Ajou University Hospital, 9Kyung-Hee University Hospital, 10Kyung Hee University Hospital at Gangdong, 11Catholic University Hospital of Daegu

Background: The natural course or clinical outcome in Korean rheumatoid arthritis (RA) patients with hepatitis C vi-

rus (HCV) infection is poorly understood. Biologic disease modifying anti-rheumatic drugs (bDMARDs) are effective for

the treatment of RA, however concerns remain regarding the safety of bDMARDs in patients with concurrent HCV

infection.

Objective: To investigate the outcomes of HCV-infected Korean RA patients who were treated with bDMARDs

Methods: A multicenter retrospective observational study was conducted at 12 university hospitals between

November 2014 and November 2015. Seventy-eight patients who met the 2010 ACR/EULAR classification criteria for

RA, and with HCV infection were identified. Baseline and longitudinal data including HCV genotype, viral load, treat-

ment, extrahepatic manifestations were obtained. The safety profile and changes of liver fuction/viral RNA titer were

evaluated. HCV reactivation was defined as having both viral and biochemical breakthrough.

Results: Mean age (SD) of diagnosis of RA was 56.2 (11.2) years, mean disease duration was 7.8 (5.0) years, and 60

patients were female (76.9%). Seventeen (21.8%) patients were treated with bDMARDs; 2 infiliximab, 8 adalimumab,

8 etanercept, 2 tocilizumab, and 1 abatacept. The mean treatment duration of bDMARDs were 9.3 months for infliximab,

30.2 months for adalimumab, 29.2 months for etanercept, 13.4 for tocilizumab, 3.8 months for abatacept. At start-up,

conventional DMARD and anti-viral therapy was concomitantly used in 11 (64.7%), 1 (9.6%) patient(s), respectively.

During the study period, one patient experienced mild elevation of HCV RNA titer. However, there was no case of HCV

reactivation.

Conclusion: Our data suggests that RA patients with HCV infection can tolerate bDMARDs without increased risk of

HCV reactivation. This contrasts with other study results in bDMARD users infected with hepatitis B virus.

Poster 31


S210

Baricitinib Versus Placebo or Adalimumab in Patients with Active Rheumatoid Arthritis and an Inadequate

Response to Background Methotrexate Therapy: Results of a Phase 3 Study

Jieon Won1, Peter C. Taylor2, Edward C. Keystone3, Désirée van der Heijde4, Yoshiya Tanaka5, Taeko Ishii6, Kahaku Emoto6, Lili Yang6, Vipin Arora6, Carol Gaich6, Terence Rooney6, Douglas Schlichting6, William L. Macias6, Stephanie de Bono6, Michael E. Weinblatt7

1Presenting on behalf of Eli Lilly and Company, Indianapolis, USA, 2Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK,

3The Rebecca MacDonald Centre, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada, 4Leiden University Medical Center, Leiden, The Netherlands, 5School of Medicine, University of Occupational & Environmental Health, Kitakyushu, Japan,

6Eli Lilly & Company, Indianapolis, USA, 7Brigham and Women’s Hospital, Boston, USA

Background: In phase 3 studies, baricitinib (bari) improved disease activity in patients (pts) with active rheumatoid

arthritis (RA) and an inadequate response to conventional synthetic or biologic disease-modifying antirheumatic drugs

(DMARDs).

Objective: The primary endpoint was ACR20 response at Wk 12 for bari vs placebo (PBO). Major secondary endpoints

included comparisons of bari vs adalimumab (ADA) for ACR20 and change in DAS28-CRP at Wk 12.

Methods: Pts with active RA despite stable background methotrexate (MTX) were randomized 3:3:2 to PBO, bari 4mg

once daily, or ADA 40 mg biweekly, stratified by region and baseline joint erosion status. Nonresponders were rescued

from Wk 16. At Wk 24, pts on PBO switched to bari.

Results: Of 1305 randomized pts, 89%, 94%, and 93% completed Wk 24 in PBO, bari, and ADA groups, respectively.

Rescue rates were 26%, 7%, and 12% for PBO, bari, and ADA, respectively. ACR20 response at Wk 12 was higher for bari

vs PBO (70% vs 40%, p≤.001). Compared to ADA, bari was superior with respect to measures including ACR20 re-

sponse and improvement in DAS28-CRP at Wk 12. Compared to PBO, daily diary measures of morning joint stiffness

duration and severity, worst tiredness, and worst joint pain were significantly improved in pts receiving bari from as early

as Wk 1. Rates of treatment-emergent adverse events, including infections, were higher for bari and ADA compared to

PBO. Compared to PBO, serious adverse event rates were similar for bari and lower for ADA; serious infection rates were

similar across groups. Two deaths occurred (bari):1 pneumonia and 1 duodenal ulcer hemorrhage. Five malignancies

were reported:2 bari and 3 PBO. There were no gastrointestinal perforations. Lab abnormalities were consistent with oth-

er phase 3 studies;few led to discontinuation.

Conclusion: Despite background MTX, once-daily bari was associated with significant clinical improvements com-

pared to PBO and ADA, with an acceptable safety and tolerability profile.

Poster 32


S211

Evaluation of the Relationship between IL-10, IL-17, IL-23 Levels and Disease Activity of

Systemic Lupus Erythematosus and Vitamin D Metabolism

Taskin Senturk1, Beyza Cetin2, Gokhan Sargin1, Neriman Aydin3

Departments of 1Rheumatology, 2Internal Medicine and 3Clinical Microbiology, Adnan Menderes Universty, Aydin, Turkey

Background: SLE is a chronic, autoimmune, inflammatory disease and the prototype of multisystem autoimmune

diseases. Several cytokines such as interleukin (IL)-10, IL-17, IL-23, and vitamin D have been suspected in the patho-

genesis of SLE. However, the association between these cytokines, vitamin D and disease activity is unknown.

Objectives: We aimed to determine the association between IL-10, IL-17, IL-23, vitamin D and SLE disease activity in-

dex (SLEDAI) score.

Methods: We included 40 patients with SLE (mean age: 35.5±13.41 years, 95% female) and 20 healthy controls (mean

age: 36.1±14.76 years, 70% female) in the study. Clinical and laboratory parameters and, SLEDAI score were evaluated.

Serum IL-10, IL-17 and IL-23 were measured by nephelometry and vitamin D by HPLC (high-performance liquid chro-

matography). Mann-Whitney U and Kolmogorov-Smirnov test were used for statistical analysis. P<0.05 was accepted as

statistically significant.

Results: The level of vitamin D was significantly lower (p=0.003), and IL-23 was significantly higher (p=0.001) in SLE

patients compared to healthy controls. There was no significant difference for IL-10 and IL-17 between both group

(p>0.05). However, a significant correlation between vitamin D and disease duration (p=0.02), and between IL-23 and

vitamin D (p=0.019) were found among SLE patients. Vitamin D levels were correlated with SLEDAI score and IL-23 in

patients group.

Conclusions: Although there are studies suppporting the role of IL-10 and IL-17 in the pathogenesis of SLE in the liter-

ature, there was no significant difference between patients and healthy controls in our study. IL-23 levels were sig-

nificantly higher, whereas vitamin D levels were significantly lower in SLE patients than in the control group. Also vita-

min D levels were negative correlated with duration of disease and IL-23. Levels of IL-23 may be used to evaluated the

disease activity, or may be a promising therapeutic approach for SLE patients.

Poster 33


S212

Comparison of the Clinical, Serological, and Prognostic Differences among Juvenile-, Adult-, and Late-onset Lupus

Nephritis in Korean Patients: A Case-control Study

Ji-Hyoun Kang, Dong-Jin Park, Yi-Rang Yim, Ji-Eun Kim, Jeong-Won Lee, Kyung-Eun Lee, Lihui Wen, Tae-Jong Kim, Yong-Wook Park, Shin-Seok Lee*

The Division of Rheumatology, The Department of Internal Medicine and Chonnam National University Medical School, Gwangju, Korea

Objectives: SLE patients present with different clinical and serological manifestations according to the age at disease

onset. However, it is not known that the association between disease onset age and the clinical presentation of lupus

nephritis (LN). We investigated whether LN patients could be distinguished based on the time of disease onset and the

groups differed in their clinical, serologic features and prognosis in Korean patients.

Methods: We enrolled 117 SLE patients with available data at the time of renal biopsy for LN from the lupus cohort

at Chonnam National University Hospital. We divided the LN patients according to the age at LN diagnosis into three

groups [juvenile-onset LN (JLN), adult-onset LN (ALN), and late-onset LN (LLN)] and compared the baseline demo-

graphic, clinical, histologic, and laboratory findings. We also compared the treatment and long-term prognosis of LN.

Results: Of the 114 LN patients, 20 (17.5%), 84 (71.8%), and 13 (11.1%) had JLN, ALN, and LLN, respectively. LLN

patients were less educated than ALN and JLN patients (p<0.001). HTN and DM at the onset of LN were more common

in LLN patients than ALN or JLN patients (p<0.001 and 0.037). LLN patients had a higher WBC count and lower eGFR

than ALN or JLN patients (p<0.011 and 0.002). Histologically, LLN patients had more chronicity indices and a higher

chronic score. Anti-Ro antibodies were found less frequently in JLN (p=0.024) and lower complement levels were more

common in JLN and less common in LLN (p<0.011 and 0.002). During a mean follow-up of 76.5 months, the develop-

ment of chronic kidney disease and death from any cause were higher in LLN patients than in JLN and ALN patients

(p=0.028 and 0.038).

Conclusions: LLN patients had more chronicity at the time of renal biopsy, and more deterioration of kidney function

and death on long-term follow-up, than JLN and ALN patients. Therefore, LLN patients should be monitored and man-

aged carefully to avoid poor outcomes.

Poster 34


S213

Body Mass Index, HDL Cholesterol, Taking NSAID, and Current Dose of Glucocorticoids Might Contribute

to Subclinical Atherosclerosis in SLE Patients with Low Disease Activity

Ju-Yang Jung, Hyun-Ah Kim, Chang-Hee Suh

Department of Rheumatology, Ajou University School of Medicine, Suwon, Korea

Background: Systemic lupus erythematosus (SLE) patients have increased risk of advanced atherosclerosis and car-

diovascular disease. While the mechanism is not completely understood, immunologic deterioration and traditional risk

factors such as overweight and dyslipidemia have been regarded to contribute.

Objectives: We tried to look for change of subclinical atherosclerosis in SLE patients and analyze the risk factors of

CVD and SLE-related characteristics with the variations.

Methods: We assessed carotid artery intima-media thickness (cIMT) and carotid artery plaque by Doppler ultra-

sonography among sixty-one female SLE patients who were enrolled in the study with subclinical atherosclerosis 4 years

ago.

Results: The mean cIMT of the patients was 0.39±0.09 mm and 11 patients had carotid plaques, which were not sig-

nificantly different with the previous study. Twenty one patients had the increased cIMT, and new carotid plaque was de-

veloped in 7 patients. The patients with increased cIMT had lower body mass index (BMI), longer disease duration, more

rarely took non-steroidal anti-inflammatory drugs (NSAID), and higher cumulative glucocorticoids dose compared with

those not. The patients with new carotid plaque development had lower high density lipoprotein (HDL) cholesterol and

higher doses of glucocorticoids. On multiple regression analysis, BMI (r=0.62, p=0.01), HDL cholesterol (r=0.94,

p=0.02), and taking NSAID (r=0.16, p=0.03) were related with cIMT increment, and current glucocorticoids dose

(r=1.14, p=0.04) were associated with plaque development.

Conclusion: The follow up study for SLE patients with low disease activity showed low BMI, low HDL cholesterol, and

not taking NSAID were associated with cIMT increment. Moreover, current glucocorticoids dose was associated with pla-

que development. Considered that mean BMI was lower than other studies, obesity paradox in cardiovascular disease risk

might support it.

Poster 35


S214

Antiphospholipid Antibody Positivity and Related Clinical Characteristics in Korean Lupus Patients

Dam Kim1, Soo-Kyung Cho1, Kyung-Eun Lee2, Dong-Jin Park2, Shin-Seok Lee2, Yoon-Kyoung Sung1

1Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, 2Division of Rheumatology, Department of Internal Medicine, Chonnam National University Medical School and Hospital, Gwangju, Korea

Background: Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by recurrent throm-

bosis and/or pregnancy morbidities in the presence of antiphospholipid antibodies (aPL). Systemic lupus erythematosus

(SLE) is the most common cause of secondary APS, however, the information about APS in SLE patients is scarce.

Objectives: In this study, we aimed to identify the prevalence of aPL and related clinical characteristics in Korean SLE

patients.

Methods: Among 505 SLE patients from KORean lupus NETwork (KORNET), we selected 469 patients who under-

went aPL tests within 2 years of enrollment. They were classified into two groups: 1) aPL (+) group as patients with at

least one aPL which includes anticardiolipin antibody (aCL), anti-ß2 glycoprotein I (anti-ß2GPI) and lupus anticoagulant

(LAC), and 2) aPL (-) groups as patients without aPL. We compared the demographic and clinical characteristics between

two groups, and clinical symptoms of thrombosis and obstetric complications were compared according to patterns of

aPL.

Results: The prevalence of aPL was 25.4% and all 3 aPL were positive in 1.7% among Korean lupus patients. Although

age, sex and autoantibody profile such as ANA and anti-dsDNA antibody were not different between two groups, ever

smokers (19.3% vs. 8.6%, p<0.01) were more common in aPL (+) group and 37.8% of aPL (+) patients were using

aspirin. More patients in aPL (+) group underwent stroke than aPL (-) group (6.7% vs. 0.9%, <0.01), whereas no differ-

ent was found in history of ischemic heart disease or spontaneous abortion.

Conclusion: Twenty five percent of patients had aPL in Korean SLE patients. In addition, stroke was more common in

patients with aPL (+) SLE patients.

Poster 36


S215

Lupus Nephritis is Associated with more Corticosteroid-associated Organ Damage but Less

Corticosteroid Non-associated Organ Damage

Young Bin Joo, MD, PhD1,2, Soyoung Won, PhD3, Chan-Bum Choi, MD, PhD1,3, Sang-Cheol Bae, MD, PhD1,3

1Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, 2Department of Rheumatology, St Vincent's Hospital, The Catholic University of Korea, Suwon, 3Clinical Research Center for Rheumatoid Arthritis (CRCRA), Seoul, Korea

Background: Lupus nephritis (LN) has been suggested to be a predictor of organ damage accrual. Since patients with

LN are more exposed to immunosuppressive agents including corticosteroid, and also have high inflammatory burdens,

they might be more vulnerable to organ damage than patients without LN.

Objective: To investigate the association of LN on organ damage and mortality.

Methods: A total of 1,112 patients with systemic lupus erythematosus (SLE) were investigated. LN was defined as a

proteinuria as represented by the 1997 American college of rheumatology (ACR) criteria. Damage was assessed using

the SLICC/ACR Damage Index (SDI). The associations of LN with overall, non-renal, corticosteroid-associated, and

non-associated damage were analyzed using logistic regression. The age-adjusted and sex-adjusted standardized mortal-

ity ratio (SMR) was evaluated in patients with vs without LN.

Results: The prevalence of LN was 46.3%. After a mean follow-up of 7.6 years, patients with LN had a higher percent-

age of overall damage than patients without LN (51.5% vs. 35.7%, p<0.001). The odds ratio was 1.40 after adjusting for

age at SLE diagnosis, sex, disease duration, anti-malarial agents, immunosuppressive agents, and cumulative cortico-

steroid dose. However, LN was not associated with non-renal damage (p=0.551). The odds of corticosteroid-associated

damage were higher (2.06, 95% CI 1.43-2.96), whereas the odds of non-associated damage were lower (0.50, 95% CI

0.35-0.75) in patients with LN. The age-adjusted and sex-adjusted SMRs of patients with vs without LN were 5.17 (95%

CI 3.49-7.38) and 2.32 (95% CI 1.47-3.48), respectively.

Conclusion: LN was associated with more overall organ damage but not more non-renal organ damage. Patients with

LN had more corticosteroid-associated damage, but less corticosteroid non-associated damage compared with patients

without LN. Additionally, the SMR of patients with LN was significantly higher than the SMR of patients without LN.

Poster 37


S216

Comparison of Clinical and Serological Differences According to the Autoantibody Cluster in Women

with Systemic Lupus Erythematosus: Results from the Korean Lupus Network (KORNET) Registry

Ji-Eun Kim, Dong-Jin Park, Ji-Hyoun Kang, Yi-Rang Yim, Jeong-Won Lee, Kyung-Eun Lee, Lihui Wen, Tae-Jong Kim, Yong-Wook Park, Shin-Seok Lee

Department of Rheumatology, Chonnam National University Medical School & Hospital Gwangju, Korea

Objectives: Individual autoantibodies are associated with the clinical features in patients with systemic lupus eryth-

ematosus (SLE). However, few studies have investigated differences in disease presentation based on autoantibody pro-

files in Asian patients with SLE. This study evaluated autoantibody clusters and compared the clinical and serological pre-

sentation and clinical outcome in Korean SLE patients.

Methods: The Korean Lupus Network (KORNET) is a nationwide multicenter, hospital-based registry, set up to pro-

spectively assess outcomes in Korean SLE patients. Of the 505 SLE patients enrolled in the KORNET registry from July

2014 to November 2015, the study group comprised 339 consecutive female SLE patients. Seven autoantibodies

(anti-dsDNA, anti-Sm, anti-RNP, anti-Ro, anti-La, lupus anticoagulant (LAC), and anti-cardiolipin antibody [aCL]) were

selected for cluster analysis using the K-means cluster analysis procedure.

Results: Three distinct autoantibody clusters were identified: cluster 1, anti-dsDNA and anti-Ro; cluster 2, anti-RNP;

and cluster 3, anti-RNP, anti-Ro, and anti-La. Compared with patients in clusters 2 (n=99) and 3 (n=85), patients in clus-

ter 1 (n=155) had a shorter symptom duration before SLE diagnosis and higher incidence of biopsy-proven lupus

nephritis. Patients in cluster 3 had a higher incidence of discoid rash, central nervous system involvement, lupus pan-

creatitis, pulmonary arterial hypertension, Raynaud’s phenomenon, and premature gonadal failure. In addition, patients

in cluster 3 had the lowest proportion of mean prednisolone>7.5 mg/day in the medication history.

Conclusion: Autoantibody clusters were associated with the clinical features in women with SLE. Clustering autoanti-

bodies could be a valuable approach for differentiating between various clinical subsets of SLE, and may help to guide pre-

diction of the subsequent clinical course and organ damage in these patients.

Poster 38


S217

Vitamin D and Bone Mineral Density in Rheumatoid Arthritis and Systemic Lupus Erythematosus

Ju-Yang Jung, Hyoun-Ah Kim, Chang-Hee Suh

Department of Rheumatology, Ajou University School of medicine, Suwon, Korea

Background: Vitamin D (VitD) has been revealed to involve immunologic pathogenesis in rheumatoid arthritis (RA)

and systemic lupus erythematosus (SLE). Moreover, Vit D plays a pivotal role in bone formation which tends to be vulner-

able in RA and SLE.

Objectives: We studied the effects of clinical features and VitD on bone mineral densities (BMD) in RA and SLE

patients.

Methods: Age matched 94 female patients with SLE and 92 female patients with RA were recruited. The medical data

including levels of 25-OH-VitD from March to May and BMD were measured by dual energy X-ray absorptiometry were

collected.

Results: The L-spine and hip T-scores were not different between RA and SLE patients, and the T-scores were not dif-

ferent between the patients with VitD deficiency and those without. In SLE, the patients with osteoporosis had higher

erythrocyte sedimentation rate (ESR) than those without osteoporosis (31.4±23.9 vs 16.4±11.9, p=0.008). Among the

patients taking VitD replacement, RA patients had lower levels of 25-OH-VitD than SLE patients (19.83±8.07 vs

24.33±10.45, p=0.011), and L-spine and hip T-scores in RA patients were lower than those in SLE patients. On multiple

regression analysis, age (r=-0.131, p<0.001), disease duration (r=-0.082, p=0.017), vitamin D replacement (r=-0.787,

p=0.003) and glucocorticoids dose (r=-0.111, p=0.024) were associated with lowest T-score of L-spines in RA patients,

while age (r=-0.058, p=0.028) and ESR (r=-0.025, p=0.005) were associated with lowest T-score of L-spines in SLE

patients.

Conclusions: There was no difference of BMD between RA and SLE, and according to VitD deficiency. In RA patients,

age, disease duration, vitamin D replacement, and glucocorticoids dose might be contributing factors for BMD. Also, age

and ESR could influence in spinal BMD in SLE.

Poster 39


S218

Salivary Proteomic Analysis in the Patients with Systemic Lupus Erythematosus

Ju-Yang Jung, Hyun-Ah Kim, Jin-Young Nam and Chang-Hee Suh


Background: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by patho-

genic autoantibodies and uncontrolled inflammatory response. As symptoms and activities changes with time, the pa-

tients with SLE need to take blood sampling to measure disease activity.

Objectives: We try to find a salivary protein composition and seek for what difference helps to discriminate and eval-

uate patients with SLE with more convenient way.

Methods: Total 80 patients with SLE and 40 healthy controls (HCs) participated, and all collected saliva in the morning

with fasting condition. Same amount of protein of two groups were prepared with pooling 10 samples from SLE patients

and HCs, and subjected to 1 and 2-dimensional gel electrophoresis (DE). The spots with more than 2 fold alteration in

expression were identified by matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) mass spec-

trometer (MS) analysis.

Results: Three hundreds eighty proteins were detected in 1 DE analysis, 13 spots were up-regulated, and 14 spots were

down-regulated in SLE than in HCs. Epidermal growth factor receptor kinase substrate 8-like protein 2 was detected only

in HCs, and galectin-7, putative helicase and transaldolase were detected only in SLE. By 2-DE analysis, 20 spots of pro-

tein were differently detected in SLE compared in HCs. Immunoglobulin gamma-3 chain C region, protein S100, Zinc-al-

pha-2-glycoprotein, BPI fold containing family a member 2 showed significantly different concentration between SLE and

HCs (p<0.05).

Conclusion: Current proteomic analysis using electrophoresis and MS analysis is accurate to detect tiny amounts of

proteins. From 1-DE and 2-DE analysis, several proteins in saliva were differently detected in SLE and HCs, suggested

that salivary protein might be useful biomarkers for SLE.

Poster 40


S219

The Increase or Decrease of Serially Assessed anti ds-DNA Antibody Serum Level is Strong Relationship

with Lupus Flare Up: Single Center Experience

Sang Yeob Lee, Sung Won Lee, Won Tae Chung

Department of Rheumatology, Division of Internal Medicine, Dong-A Uiversity

Introduction: Patients with Systemic Lupus Erythematosus (SLE) may experience flare of disease activity. The aim of

this study was to assess flares clinical features, focusing on the relationship with serially assessed anti-double stranded

DNA antibodies (anti-dsDNA) serum levels by Farr assay, through the analysis of a monocentric cohort of SLE patients

and a literature review.

Methods: We analyzed 159 patients who visited outpatients or admitted to Dong-a university hospital between march

2012 and march 2015. They were diagnosed to SLE, according to the revised 1997 ACR criteria and serillay assessed se-

rum anti-dsDNA every three months. Among subjects, 62 subjects were excluded because of drop-out. So 97 patients

were enrolled and section to three groups. The one group, 29 patients were showed significant increase or decrease serum

anti-dsDNA level, the other group, 33 patients who maintained high level anti-ds-DNA, another group, 35 patients were

maintained lower level anti-ds-DNA. Informed consents were obtained from all individual participants included in the

study.

Results: The mean SLEDAI score was 4.21 (±4.63) in 29 patients who were showed significant increase or decrease

serum anti-dsDNA level. On the contrary, mean SLEDAI score was low in no change anti-ds-DNA level group {0.47

(±5.33) in high keeping anti-ds-DNA group (p=0.000), 0.51 (±2.03) in low keeping anti-ds-DNA group (p=0.00)}. The

14 patient who were increased serum anti-dsDNA level, had hematologic and cardiopulmonary exasperation. 15 pa-

tients, who were decreased serum anti-dsDNA level, had worsened musculoskeletal and mucocutaneous manifestation.

Conclusion: The increased SlEDAI score is associated with change anti ds-DNA antibody level and increased an-

ti-ds-DNA level subjects had more severe clinical manifestation than decreased anti-ds-DNA level subjects.

Poster 41


S220

Outcomes in Patients with Ischemic Stroke Regarding Titer and Persistence of Antiphospholipid Antibodies

Jung Yoon Pyo, Sang-Won Lee, Jason Jungsik Song, Yong-Beom Park

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea

Background: Stroke and transient ischemic attack (TIA) are the most common neurologic manifestation of anti-

phospholipid syndrome (APS). The international consensus criteria for APS classification require persistent anti-

phospholipid antibodies (aPL) positivity and medium or high titer for anticardiolipin antibody (aCL) associated with

clinical manifestations[1]. However, significance of persistence and titer of aPL on the clinical relevance is not identified.

Objectives: To evaluate the effect of persistent and medium or high titer of aPL positivity on recurrence in patients with

ischemic stroke/TIA.

Methods: We reviewed medical records of 99 patients with ischemic stroke/TIA who had at least one or more positive

aPL (ie, positivity for aCL, β2-GPI, LA). We divided these patients into two groups according to the most recent revised

classification (Sydney consensus conference), and designated as “definite APS” who fulfilled the laboratory criteria, and

“aPL carriers” who had transient or low titer aPL. We compared the subsequent ischemic stroke/TIA events between the

two groups.

Results: Of the 99 patients, 46 (46%) were classified as definite APS and 53 (54%) as aPL carriers. There was no in-

creased risk of subsequent ischemic/TIA events in definite APS group compared with aPL carriers group. The overall

event was 14 (30.4%) in APS group and 16 (30.2%) in aPL carriers group during 60.4 months and 43.8 months follow

up period respectively. 38 patients were having anticoagulation for treatment and 60 patients were on anti-platelet treat-

ment without anticoagulation, but there was no difference on recurrence events regarding the treatment.

Conclusions: Diagnosing definite APS does not predict increased risk for subsequent ischemic stroke/TIA.

Anticoagulation does not reduce the risk of recurrence compared with anti-platelet agents in patients with ischemic

stroke/TIA with positive aPL.

Poster 42


S221

Cytomegalovirus Reactivation in Patient with Active Lupus Nephritis

Hyunae Lee, yeunmi Kang, Jihyun Han, Sangyoon Kim, In Je Kim, Jisoo Lee

Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea

Cytomegalovirus (CMV) infection can be life-threatening in immunocompromised patients. There are only a few re-

ports on CMV reactivation in systemic lupus erythematosus (SLE). We report a rare case of CMV reactivation, which de-

veloped after immunosuppressive therapy in a 26-year-old woman with severe lupus nephritis. This patient who was on

high-dose prednisolone and cyclophosphamide induction therapy developed high fever, dyspnea, and diarrhea. CMV an-

tigen was positive, and she was diagnosed with CMV pneumonia and CMV colitis. Clinical improvement was observed

after ganciclovir treatment. Despite the improvement of disease activity, she again presented with fever and

pancytopenia. Rising CMV titers were detected and it was considered as CMV reactivation. Clinical course of lupus neph-

ritis should be carefully monitored for development of CMV infection. CMV titer in a SLE patient with fever and pan-

cytopenia may be a useful marker for early detection of CMV infection, even after first remission of it.

Poster 43


S222

A Case of Systemic Lupus Erythematosus Presenting as Stevens-Johnson Syndrome

Mi-Hye Kwon, Chung-Il Joung

Department of Internal medicine, Konyang University College of Medicine, Daejeon, Korea

Systemic lupus erythematosus has myriads of clinical manifestations, the skin involvement is known as the second

common form of disease. Among diverse skin manifestations, acute cutaneous lupus erythematosus (ACLE) is usually

observed in the area exposed to the light, such as face, but rarely, generalized distribution may occur. A hyper-acute form

of ACLE can simulates Stevens-Johnson syndrome (SJS) or toxic epidermal necrosis.

A 33-year-old man presented with erythematous eroded papules and patches on head, neck and upper chest for more

than 2 months (Fig. 1). He also presented hemorrhagic erosion with crust on lips, buccal and nasal mucosa accompanied

by conjunctival injection. Skin biopsy showed mild degree of vacuolar alteration and thickening of basement membrane,

perivascular and periadnexal lymphohistiocytic infiltration and stromal mucin deposition (Fig. 2). On direct immuno-

fluorescence, there were Ig G and Ig M deposition along the basement membrane zone. Laboratory findings demon-

strated pancytopenia, and positivity for ANA, Anti-dsDNA, and anti-Ro. The patient was diagnosed SLE according to

clinical, histological, and laboratory findings. He was treated with oral methylprednisolone 0.5mg/kg/day and hydroxy-

chloroquine, all the skin manifestations had subsided in 2 months. He later developed proteinuria and was diagnosed as

lupus nephritis class V by renal biopsy. Herein we report a rare case of SLE presenting as SJS.

Poster 44


S223

Renal Microaneurysm in a Patient with Systemic Lupus Erythematosus

Jung Su Eun, Eun Song Lee, Jong Wan Kang, Na Ri Kim, Sang Jin Lee, Young Mo Kang, Eon Jeong Nam

Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea

Systemic lupus erythematosus (SLE) is a complex, heterogeneous disease characterized by autoantibody production

and potential involvement of nearly every organ system. Although vasculitis usually confined to small vessels is a fairly

common feature of SLE, necrotizing vasculitis with aneurysm is an uncommon feature. Especially, renal arterial aneur-

ysm has been very rarely reported in patients with SLE. We experienced a case of renal microaneurysm in a patient with

SLE.

Case: A 41-year old woman who was previously diagnosed with hypertension, hypertensive retinopathy admitted to

our hospital with both foot metatarsophalangeal (MTP) joint pain. She did not complain of flank pain. On physical ex-

mination, both MTP joint revealed mild swelling and tenderness. Fundoscopic examination showed small hard exudates

in the left retina. Laboratory examination revealed the following : lymphocyte 1330/mm3, immunoglobulin G 2354

mg/dl (700-1600), serology for antinuclear antibodies, anti-double-stranded DNA, anti-β2-glycoprotein were positive.

Serum complement levels and urinalysis were normal. She was diagnosed with SLE based on clinical feature (arthritis)

and laboratory findings. Additionally, abdominal computed tomographic (CT) scan showed multiple wedge-shaped areas

on both kidney. She underwent a renal angiography which demonstrated bilateral multiple reanl artery microaneurysms.

Renal biopsy was done to check for renal parenchyma. Renal biopsy revealed well-demarcated parenchymal atrophic

change without glomerular proliferation or sclerosis that suggests ischeminc nephropathy. For treatment of renal vasculi-

tis with microaneurysm, she was treated with high dose glucocorticoid and mycophenolate mofetil. Six months later,

there was improvement of hypertension, hypertensive retinopaty, arthritis. She is scheduled to be examined abdominal

CT and renal angiography soon.

Conclusions: We suggest that visceral vasculitis should be included in the work-up of patients with SLE.

Poster 45


S224

A Case of Meningoencephalitis by Cryptococcus Neoformans in a Patient with Systemic Lupus Erythematosus

Do Sik Moon1, Hyun-SooK Kim2, Yun Sung Kim1

1Department of Internal Medicine, Chosun University College of Medicine, Gwanju, 2Department of Internal Medicine, Sunchun Hyang University College of Medicine, Seoul, Korea

Invasive fungal infection can be a lethal complication in systemic lupus erythematosus (SLE).

Crytococcus neoformans, as one of the most common pathogenic species worldwide, can cause infection disease in

human. The central nervous system (CNS) is a common site for cryptococcal infection which usually presents crypto-

coccal meningitis. The cryptococcal meningitis is a recognized complication of SLE, with high mortality rates, particularly

in those treated with immunosuppressive agents. However, it is difficult to differentiate infectious meningitis and neuro-

psychiatric lupus because of the clinical manifestations are unspecific and frequently are confused with lupus activity. So

a early diagnosis and treatment is very important for its significant mortality and morbidity. We report the case of fatal

meningoencephalitis by Cryptococcus neoforman in a 44 years old patient with SLE

Poster 46


S225

Long-term Outcomes of Autologous Peripheral Blood Stem Cell Transplantation for Refractory Rheumatic Diseases

Seung Lee, Jae-Bum Jun, Chan-Bum Choi, Sang-Cheol Bae

Hanyang University Hospital for Rheumatic Diseases

Objectives: We investigated long-term outcomes of autologous peripheral blood stem cell transplantation (PBSCT) for

treatment of refractory rheumatic diseases.

Methods: Patients who underwent PBSCT for refractory rheumatic diseases at our hospital between 2002 and 2005

were assessed for outcomes including treatment response in disease activity at, damage, adverse events, and survival at

6 months and either July 2015, last follow-up, or at death.

Results: A total of 11 patients including 6 systemic lupus erythematosus (SLE), 4 systemic sclerosis (SSc), and 1 Still's

disease were treated with PBSCT. Lupus nephritis and neuropsychiatric lupus were the manifestations refractory to con-

ventional treatments requiring PBSCT in the SLE patients. At 6 months, complete response was observed in 2 patients,

partial response in 2, and 2 patient expired. One patient who expired showed a complete response at 2 months after trans-

plantation but discontinued all treatment at the patient’s discretion and expired at 6 months due to flare. Long-term out-

comes showed 2 patients in remission without organ damage, 1 in remission with organ damage, and 1 in low disease

activity with organ damage. Of the 4 patients with SSc, 2 showed complete response, 1 partial response, and 1 trans-

plantation-related death at 6 months. In the long-term, 2 remained in remission without relapse, 1 expired and 1 was lost

to follow up. The Still’s diseases patient showed partial response at 6 months and was in remission in long-term

assessment.

Conclusion: At 6 months after PBSCT for refractory rheumatic diseases, 5 patients showed complete response, 4 parti-

al response, and 3 expired. Four patients showed relapse in the long-term. 2 of them went back in remission and 1 patient

expired. Ten year survival rate was 70% with 40% recurrence rate and 20% treatment-related mortality rate.

Poster 47


S226

Tuberculin Skin Test and Interferon Gamma Release Assay (IGRA) for Diagnosing Latent Tuberculosis Infection in Patients

with Systemic Lupus Erythematosus

Hyoun-Ah Kim, Hundo Cho, Ye Won Kim, Ju-Yang Jung, Yoo-Jin Um, Jin-Hee Jung, Chang-Hee Suh


Objective: We investigated the agreement between the tuberculin skin test (TST) and the QuantiFERON-TB Gold

(QFT-G) assay in the diagnosis of latent tuberculosis infection (LTBI) in patients with systemic lupus erythematosus

(SLE). Furthermore, we evaluated the factors associated with indeterminate results in the QFT-G assay in patients with

SLE.

Methods: We enrolled 136 patients with SLE prospectively, and compared them to 66 patients with rheumatoid arthri-

tis (RA). In addition to the TST, QFT-G assay, patients’ medications, and Bacillus Calmette-Guérin (BCG) vaccination

status were also investigated. A positive TST or QFT-G assay result without an active tuberculosis lesion on chest x-ray

was considered to indicate a diagnosis of LTBI.

Results: The prevalence of LTBI was 26.5% in patients with SLE and 30.3% in patients with RA. The agreement be-

tween the TST and QFT-G assay was fair in SLE patients, but, poor in RA patients. BCG vaccination was one factor asso-

ciated with discordance between TST and QFT-G. Older age and higher SLE Disease Activity Index (SLEDAI) score were

associated with a negative TST/positive QFT-G result in patients with SLE. Higher SLEDAI score and increased gluco-

corticoid dose were associated with an indeterminate result in the QFT-G assay for patients with SLE.

Conclusions: Agreement between the QFT-G assay and TST in patients with SLE was found to be fair. However, BCG

vaccination status, age, and SLEDAI score are all factors that could result in discordance between the two tests.

Indeterminate results from the QFT-G assay may be caused by a higher SLEDAI score or increased glucocorticoid dose.

Poster 48


S227

Association of HLA Genes in Systemic Sclerosis with Interstitial Lung Disease

Hyun Mi Kwon1*, Eun Young Song2*, Ye Ji Lee3, Jin Kyun Park1, Eun Young Lee1, Yeong Wook Song1, Eun Bong Lee1

1Division of Rheumatology, Department of Internal Medicine, 2Department of Laboratory Medicine, 3Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea

Background: Interstitial lung disease (ILD) is related to significant morbidity and mortality in systemic sclerosis (SSc).

Many studies have reported the association of human leukocyte antigen (HLA) alleles with SSc, but few have focused on

SSc subpopulation with ILD.

Objectives: The aim of this study was to investigate the association of HLA class I and HLA class II with ILD in Korean

SSc cohort.

Methods: A total of 170 SSc patient were enrolled at Seoul National University Hospital from 1988 to 2014. Two hun-

dred one1 healthy participants from Korean Marrow Donor Program (KMDP) were recruited as controls. SSc patients

were characterized for demographic information, clinical skin subset (limited vs. diffuse), SSc-specific autoantibodies

(anti-topoisomerase I (ATA), anti-centromere (ACA), anti-ribonucleoprotein (RNP)), and internal organ involvement

(ILD, pulmonary arterial hypertension, gastrointestinal, renal involvement). One hundred five SSc patients with ILD and

65 without ILD were identified based on the findings of the chest computed tomography. HLA-A, -B, -C, -DQB1, -DRB1,

and -DPB1 typing were performed PCR amplification with directly sequencing from extracted genomic DNA.

Results: HLA-B*52:01, C*12:02, DRB1*15:02, DPB1*09:01, and DPB1*13:01 alleles were more frequently found in

SSc patients with ILD than healthy controls. However, the frequencies of these genes did not show significant difference

between SSc patients with and without ILD (Table). ATA positive SSc was associated with HLA-B*52:01, C*12:02,

DRB1*15:02, DPB1*09:01, and DPB1*13:01 alleles compared to ATA negative SSc and DPB1*09:01 showed the highest

odds ratio for ATA (OR=23.08).

Conclusion: SSc patients with ILD have several specific HLA genes compared with healthy controls and the frequencies

of these HLA genes were significantly higher in ATA-positive SSc. These results suggest shared genetic origin of HLA

class I and II between ILD and ATA positivity in SSc patients.

Table 1. HLA frequencies in patient with systemic sclerosis with ILD and without ILD compared to healthy controls

HLA allelesSSc_Total (N=170)

ILD(+)SSc (n=105)

ILD(-)SSc (n=65)

Control (N=201)

SSc Total vs. Control ILD(+)SSc vs. Control ILD(-)SSc vs. Control

Pc Pc Pc

B*52:01 23 (13.5) 20 (19.0) 3 (4.6) 9 (4.5) 0.076 <0.001 1.000 C*12:02 23 (13.5) 20 (19.0) 3 (4.6) 9 (4.5) 0.046 <0.001 1.000 DRB1* 15:02 29 (17.1) 24 (22.9) 5 (7.7) 14 (7.0) 0.074 <0.001 1.000 DPB1* 09:01 22 (12.9) 18 (17.1) 4 (6.2) 9 (4.5) 0.045 <0.001 1.000 DPB1* 13:01 52 (30.6) 38 (36.2) 14 (21.5) 25 (12.4) <0.001 <0.001 1.000

Abbreviation: HLA, human leukocyte antigen; SSc, systemic sclerosis; ILD, interstitial lung disease; OR, odds ratio; Pc, corrected P by Bonferroni correction.Pc of ILD(+)SSc vs. ILD(-)SSc: HLA-B*52:01 (Pc=0.304), C*12:02 (Pc=0.184), DRB1*15:02 (Pc=0.407), DPB1*09:01 (Pc=0.570), DPB1*13:01 (Pc=0.660).

Poster 49


S228

Metabolomics for the Diagnosis of Systemic Sclerosis

Kyong-Hee Jung1*, Sehyun Oh2, Won Park1, Mie Jin Lim1, Seong Ryul Kwon1, Sunghyouk Park2*1Division of Rheumatology, Department of Internal Medicine, College of Medicine, Inha University, Incheon,

2College of pharmacy, Seoul National University, Seoul, Korea

Background: Systemic sclerosis (SSc) is a complex multi-organ autoimmune disease that is caused by inflammation,

vasculopathy and fibrosis. Clinical heterogeneity, unpredictable course, high mortality and resistance to treatment make

physicians still frustrated. Recently, there are unmet needs of useful biomarkers for diagnosis, disease activity and se-

verity of SSc. Metabolomics is expected to be a useful tool for the identification of biomarkers and new therapeutic

targets. Several researchers have applied metabolomics to autoimmune diseases such as systemic lupus erythematosus,

and rheumatoid arthritis.

Objective: To identify the biomarker candidates for the diagnosis of SSc using metabolomic analysis.

Methods: Fifty-five patients (48 females (87 %); mean age 59.30±11.44 years; disease duration 6.92±4.36 years; 11

diffuse cutaneous SSc, 44 limited cutaneous SSc) and thirty age, gender matched healthy controls (HCs) were enrolled.

Serum samples after 8 h of fasting were stored at -80oC and analysed using nuclear magnetic resonance (NMR)-based

metabolomics.

Results: Multivariate analysis showed metabolic differences between SSc and HCs using partial least squares discrim-

ination analysis (PLS-DA: R2Y=0.654, Q2=0.482) and orthogonal partial least squares discrimination analysis

(OPLS-DA: R2Y=0.83, Q2=0.674). We identified nine discriminatory metabolites (p<0.05): isopropanol, lactate, 2-ox-

oisocaproate, glucose, and formate were increased and pyruvate, glutamate, methylguanidine, and methanol were de-

creased in SSc compared with those in the HCs. Using these metabolites for diagnosis of SSc, sensitivity was 96.36% and

specificity was 80% by Leave-one-out analysis.

Conclusion: There are considerable differences in the serum metabolomic characteristics between SSc and HCs. We

expect that metabolomic analysis can be a useful tool for identification of potential diagnostic biomarkers of SSc.

Poster 50


S229

Neutrophil/Lymphocyte Ratio (NLR) were Useful Marker in Prediction of Lung Involvement

in Patient with Systemic Sclerosis

Won-Seok Lee, Yun-Jung Choi, Yu-Mi Lee, Wan-Hee Yoo

Division of Rheumatology, Department of Internal Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea

Background: Both neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte (PLR) are reported to be in-

creased in various inflammatory diseases, but there clinical significance in systemic sclerosis (SSc) remains unclear.

Objective: The aim of the study is to evaluate usefulness of neutrophil to lymphocyte ratio in diagnosis of systemic scle-

rosis and in prediction of lung involvement such as pulmonary fibrosis.

Method: The medical records of 88 SSc patients and 50 healthy controls were retrospectively reviewed. NLR, PLR be-

tween SSc patients and healthy controls were compared, and correlation between these indexes and lung involvement

were analyzed. Exclusion criteria included active infection and/or the presence of any hematological, cardiovascular or

metabolic disorder.

Results: The NLR and PLR were found to be significantly higher in SSc patients when compared to the healthy control

(NLR: 3.95±6.59 vs 2.00±1.07, p<0.01, PLR: 163.87±101.12 vs 126.33±42.31, p<0.05). SSc patients with lung in-

volvement had higher NLR and PLR levels than those without lung involvement (p<0.01, p<0.05). NLR was negatively

correlated with forced vital capacity (FVC)(r=-0.341, p<0.01) but not diffusing capacity for carbon monoxide (DLCO).

Receiver-operating characteristics analysis (ROC) of NLR to predict lung involvement in SSc showed that the area under

the curve (AUC) was 0.763. The cut-off NLR value for prediction of lung involvement was determined as 2.59.

(sensitivity, 0.700;specificity, 0.729; p<0.01)

Conclusion: NLR may be a promising marker that reflects lung involvement in patients with SSc and values greater

than 2.59 were useful in prediction of lung involvement

Poster 51


S230

Renal Involvement in Patients with Inflammatory Myopathies in Korea

Howook Jeon, Min Seok Choi, Jeniffer Lee, Sung-Hwan Park

Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea

Background: Renal involvement in patients with inflammatory myopathies (IM) is previously thought to be

uncommon. But recently some studies suggest that two types of renal involvement occur in nealy 20% patients, one is

acute kidney injury (AKI) at diagnosis and the other is chronic kidney disease (CKD). And some possible risk factors are

proposed.

Objectives: To investigate the incidence and prognosis of renal involvement Korea, patients with IM include dermato-

myositis (DM) and polymyositis (PM)

Methods: Clinical and laboratory data of 50 patients diagnosed with IM in our rhematology clinic between 2005 and

2015 were investigated. These data were obtained from medical records and studied retrospectively. AKI was defined as

an acute doubling of serum creatinine level, and CKD as decreased GFR less than 60 ml/min/1.73m2 over 3 months. And

other renal involvement such as proteinuria more than 300 mg/day or microscopic hematuria were evaluated.

Results: The incidence and clinical manifestations of renal involvement our patients were distinguished from previous

other countries' studies. There were no patients with AKI at initial diagnosis and also no one progressed to CKD. But 16%

of patients were showed proteinuria or hematuria, suspicious of chronic glomerulonephritis and they have no other pos-

sible causes for renal involvement. We tried to conduct renal biopsy for patients with proteinuria over 1g/day, but un-

fortunately, no one agreed for procedure so we did not identify the causes of renal involvement. And we conducted stat-

istical analysis to identify risk factors for renal involvement, but all of variables - age at IM onset, sex, type of IM, under-

lying disease, various muscle enzyme levels - had no statistical significance.

Conclusion: We found that there were many patients with renal involvement presenting proteinuria or hematuria. So

when treat the patients with DM/PM, we have to monitor renal function and urinalysis, and consider renal biopsy.

Poster 52


S231

Renal Involvement in Polymyositis: A Case Report

Yoon Jeong Oh1, Eun Sung Park1, Mi Jang2, Jeong Hae Kie3, Jason Jungsik Song1, YongBeoum Park1, Chan Hee Lee4, Jin Su Park4

1Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, 2Department of Pathology, Yonsei University College of Medicine, Seoul, 3Department of Pathology, NHIS Ilsan Hospital, Goyang,

4Division of Rheumatology, Department of Internal Medicine, NHIS Ilsan Hospital, Goyang, Korea

Polymyositis (PM) is a chronic inflammatory disorder that mainly involves muscles. The systemic organ involvements

of PM including the respiratory and gastrointestinal tracts are frequently observed, however, renal involvement is rare.

Herein, we report a rare case of PM combined with immunoglobulin A (IgA) nephropathy.

A 56-year-old woman presented with a 1-month history of pruritus, weight gain (3 kg for a month), grade II bilateral

pretibial pitting edema and generalized myalgia. Laboratory tests revealed creatinine kinase (CK)=8,493 IU/L, albu-

min=2.5 g/dL and the spot urine protein/creatinine ratio=2066.9 mg/g. She was suspected as a polymyositis based on

clinical and biochemical tests, and it was confirmed on muscle biopsy (Fig. 1). Renal biopsy was also performed to eval-

uate the proteinuria. Light and immunofluorescence microscopic findings were compatible to IgA nephropathy (Haas'

subclass II) (Fig. 2). Although she has been initially treated with oral prednisolone 60 mg/day, CK showed no signs of

normalization and the severity of proximal muscle weakness worsened from grade IV to grade II.

Even though methylprednisolone pulse therapy (1 g/day, 3 times) and then cyclophosphamide pulse therapy were tak-

en, her muscle weakness persisted. Intravenous immunoglobulin was adopted in a dose of 2 g/kg for 5 days for the control

of refractory PM. After that, the patient’s proximal muscle strength has gradually improved from grade II to grade IV and

muscle enzyme was reduced (CK=780 IU/L). In addition, the amount of proteinuria was decreased. She was maintained

with oral prednisolone and regularly followed up.

Poster 53


S232

Drug Survival of TNF Alpha Inhibitor in Spondyloarthropathies Using 10 Years

of Nationwide Data in Korea: A Population-based Study

Eunyoung Emily Lee1, Jeong Seok Lee1, Yeong Wook Song1, Hee Young Lee2, Eun Young Lee1*1Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Seoul,

2Center for Preventive Medicine and Public health, Seoul National University Bundang Hospital, Seongnam, Korea.

Background: Tumor necrosis factor-alpha inhibitors (TNFi) have consistent efficacy in controlling disease activity of

spondyloarthropathies (SpA). However, real-world issues in clinical practice remain unresolved especially selecting or

switching TNFi for individual patient.

Objectives: To describe patterns of prescribing TNFi in SpA patients, we used the national health insurance claim data

of Korea from 2004 to 2013. We aimed to evaluate 1) the first choice 2) drug retention rate and duration and 3) switching

rate and duration before switching of each TNFi.

Methods: We used retrospective cohort data by the National Health Insurance Service in Korea, which consisted of

more than one million subjects representing whole Korean population followed from 2004 to 2013. All SpA patients with

any experience of TNFi were involved.

Results: One-hundred and sixty patients were found to experience any of TNFi. Etanercept was the most frequent

choice as first TNFi (39.4%). Retention rate was consistently higher for etanercept than others till 24 months (Fig 1A).

Etanercept and infliximab had longer duration of use than adalimumab. Switching rate of etanercept (8.8%) was lower

than adalimumab (11.9%) and infliximab (13.3%). Etanercept users (1.67 years) had longer duration of use before

switching than adalimumab (0.82 years, p=0.013).

Conclusions: This research can be a pilot study before analyzing nationwide cohort encompassing whole population

of Korea. Conclusively, in the aspect of drug survival of TNFi, etanercept was prescribed longer in general and the rate

of retention till 2 years was also higher than adalimumab and infliximab for 10 years after national insurance coverage.

Poster 54


S233

Lateral Spine BMD Measurement and Trabecular Bone Score Can Represent a Bone Loss in Patients

with Advanced Ankylosing Spondylitis

Min Kyung Chung, Jung Hee Koh, Jennifer Lee, Seung-Ki Kwok, Sung-Hwan Park, Ji Hyeon Ju

Division of Rheumatology, Department of Internal medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea

Backgrounds: It is well known that osteoporosis is paradoxically common in patients with ankylosing spondylitis (AS)

in spite of their new bone formation and extraosseous calcification. However, some features of advanced disease such as

syndesmophyte can influence in the result of bone marrow density (BMD) according to the measurement methods.

Objective: The aim of this study was to identify suitable BMD measurement methods reflecting bone mass loss in pa-

tients with AS.

Methods: Fifty-four patients with AS (38 males, 16 females) who assessed BMD using dual-energy X-ray absorptiom-

etry (DXA) were retrospectively reviewed. BMD was measured by anterior-posterior (AP) L1-L4, lateral (Lat) L2, L3, and

proximal femur projection. Trabecular bone score (TBS) L2-L4 was calculated as an indicator of vertebral fracture risk.

Radiologic variables including Bath Ankylosing Spondylitis Radiology Index for the spine (BASRI-s) score, modified

Stroke Ankylosing Spondylitis Spine Score (mSASSS), and the presence of syndesmophyte were determined. AS patients

were divided into mild, moderate, and advanced stages according to each radiologic variables, and the BMD measured by

different methods were compared among those 3 groups using ANOVA.

Results: Radiologic progression of AS patients represented by BASRI-s, mSASSS, and the number of syndesmophyte

was negatively correlated with Lat-L3 BMD (r=-0.431, r=-0.364, r=-0.464) and with TBS (r=-0.352, r=-0.355,

r=-0.382). Moreover, patients in advanced stage (BASRI-s≥3, mSASSS≥10, syndesmophyte≥1, respectively) showed

significantly lower Lat-L3 BMD (P=0.047, P=0.012, P=0.006) and TBS (P=0.050, P=0.014, P=0.090) compared with

those in mild stage, while they displayed no difference in conventional BMD from AP and femur DXA.

Conclusions: The Lat-L3 BMD and TBS have higher potency to mirror a bone loss in AS patients independent of their

radiologic changes. Further studies evaluating TBS cutoff value for expecting vertebral fracture are needed.

Poster 55


S234

Quantitative Assessment of Bone Marrow Fat Using Magnetic Resonance Imaging in Patients with Spondyloarthritis

Bon San Koo1*, Yoonah Song2*, Kyung Bin Joo2, Seunghun Lee2, Tae-Hwan Kim3 1Division of Rheumatology, Department of Internal Medicine, Konkuk University College of Medicine, Chungju,

2Department of Radiology and ³Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea*These two authors contributed equally.

Background/Objectives: Fat metaplasia in the bone marrow is an indicator of disease progression in spondyloarthritis

(SpA). This study sought to evaluate the degree of bone marrow fat metaplasia in patients with SpA. In order to do so,

we used two-point mDIXON fat-water separation sequences on MRI to measure the fat fraction (FF) and identify the FF

changes according to disease progression.

Methods: A total of 140 patients with SpA who had undergone pelvic MRI between September 2014 and March 2015

were retrospectively evaluated. Fat metaplasia was quantified on the FF maps using the two-point mDixon technique.

Based on the fat deposition signal on T1- and T2 weighted images, we defined three groups with high fat deposition, as

follows: 1) postinflammatory fat deposition; 2) normal marrow fat; and 3) active inflammatory area (or those with bone

marrow edema).

Results: The mean patient age was 32.2±11.6 years. A total of 84 were male (65%). The mean right and left SI joint

grades on the radiograph were 1.7±1.3 and 1.8±1.3, respectively. The mean FF of postinflammatory fat deposition area

was 82.6%±9.6% in the right and 82.2%±9.8% in the left. The mean FF of the normal marrow area was 50.4%±10.1%

in the right and 51.9%±10.4 % in the left. The mean FF of the active inflammatory edema area was 15.8±6.7 in the right

and 14.0±6.3 in the left. There was a significant correlation between the postinflammatory fat deposition areas in the SI

joint grades on the radiographs (r=0.298, p=0.005 in right and r=0.417, p=<0.001 in left). However, no correlation was

found between the FFs of the normal fat marrow area, the active inflammatory edema area, and the SI joint grade on the

radiographs.

Conclusion: The postinflammatory FF of the bone marrow increased in SpA patients who demonstrated chronic radio-

graphic changes of the SI joint. Quantitative assessment of the FF using MRI might represent a useful technique to eval-

uate SpA progression.

Poster 56


S235

Clinical Characteristics of Korean Psoriatic Arthritis Patients: Results from the Nationwide KOBIO Registry

Hyoun-Ah Kim1, Seongjun Ha2, Seoungjae Choi3, Shin-seok Lee4, Inkyung Jung5, Kichul Shin2

1Department of Rheumatology, Ajou University School of Medicine, 2Division of Rheumatology, Department of Internal Medicine, SMG-SNU Boramae Medical Center, 3Division of Rheumatology, Department of Internal Medicine, Korea University College of Medicine,

4Divison of Rheumatology, Department of Internal Medicine, Chonnam National University Medical School and Hospital, 5Department of Biostatistics and Medical Informatics, Yonsei University College of Medicine

Background: Although the clinical characteristics and manifestations of psoriatic arthritis (PsA) have been vastly stud-

ied in western countries, clinical research on Korean PsA patients are scarce. The aim of this study was to investigate the

clinical characteristics of PsA patients enrolled in the nationwide KOBIO registry.

Methods: This was an observational study of patients with PsA registered in KOBIO between 2013 and 2015. Clinical

characteristics at enrollment, previous medications before using biologics, imaging and laboratory data were obtained in

34 patients. We also compared the results with data from anklyosing spondylitis (AS) patients (n=1058) enrolled in

KOBIO during the same period. AS patients with psoriasis (PSO) and PsA with SpA were grouped as SpA with PsO for

subanalysis.

Results: Fifteen PsA patients (44.1%) were female, and the mean age was 53.3 years. Their disease duration was

4.7±5.6 years. Seven PsA patients (20.6%) had HLA-B27. Symmetric polyarthritis was the most common manifestation

(35.3%), followed by SpA (29.4%) and others. Commonly used drugs before biologics were methotrexate (88.6%), sulfa-

salazine (64.7%), and hydroxychloroquine (14.7%). We then compared clinical characteristics in PsA with SpA (n=16),

PsA without SpA (n=18), and AS with PsO (n=29). HLA-B27 was positive in PsA without SpA (16.7%) and PsA with

SpA (25.0%), lower than AS with PsO (86.2%) as expected. Positivity of HLA-B27 in AS without PsO was even higher

(91.4%). Peripheral joint involvement and dactylitis were greater in SpA with PsO than without PsO (p=0.0114 and

0.0002, respectively). Yet, the grade for sacroiliitis, if present, was lower in SpA with PsO than without PsO (p=0.0396).

Conclusion: The clinical characteristics of PsA patients in KOBIO are similar to what we see in the literature. SpA is

not an infrequent manifestation of PsA in Korea. However, the degree of sacroiliitis is largely lower than AS, thus could

be overlooked.

Poster 57


S236

Andersson Lesions of Whole Spine Magnetic Resonance Imaging Compared with Plain Radiography

in Ankylosing Spondylitis

Seong-Kyu Kim1, Kichul Shin2, Yoonah Song3, Seunghun Lee3, Tae-Hwan Kim4

1Division of Rheumatology, Department of Internal Medicine, Arthritis and Autoimmunity Research Center, Catholic University of Daegu School of Medicine, Daegu, 2Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul,

3Department of Radiology, Hanyang University Hospital for Rheumatic Diseases, Seoul, 4Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea

Objective: The objective of this study was to identify the characteristics of Andersson lesions in ankylosing spondylitis

(AS) using whole spine magnetic resonance imaging (MRI).

Methods: A total of 62 patients with AS who had undergone whole spine MRI and plain radiography were retro-

spectively enrolled in this study. We compared the number of discovertebral units (DVUs) with Andersson lesions with

clinical and radiographic indices such as erythrocyte sediment rate (ESR), C-reactive protein (CRP), the Bath Ankylosing

Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), and modified

Stoke Ankylosing Spondylitis Spine Score (mSASSS).

Results: Fifty-three patients (85.5%) by whole spine MRI and 23 patients (37.1%) by plain radiography had at least

one Andersson lesion. We found 129 DVUs with Andersson lesions (9.0%) by MRI and 35 DVUs by plain radiography

over all the spine levels. Andersson lesions by MRI were most commonly detected at the lower thoracic spine (from T7-8

to T12-L1). Among the 151 total Andersson lesions by whole spine MRI, 41 were identified as central disc type, 26 as

anterior peripheral disc type, 44 as posterior peripheral disc type, and 40 as diffuse disc type. However, the number of

Andersson lesions did not correlate with ESR, CRP, BASDAI, BASFI, or mSASSS (p>0.05 for all).

Conclusion: Our study indicates that the presence of Andersson lesions in patients with AS is clearly underestimated.

MRI is a superior technique for detecting early Andersson lesions compared with plain radiography.

Poster 58


S237

Estrogen is Associated with Radiographic Progression in Ankylosing Spondylitis

Hyemin Jeong1, Eun Kyoung Bae2, Yeong Hee Eun1, In Young Kim1, Hyungjin Kim1, Joong Kyong Ahn3, Jaejoon Lee1, Eun-Mi Koh1, Hoon-Suk Cha1

1Department of Medicine, Samsung Medical Center, 2Samsung Biomedical Research Institute, 3Kangbook Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea

Introduction: This study aimed to evaluate the role of estrogen in the radiographic spinal progression in patients with

ankylosing spondylitis (AS).

Method: One hundred and two patients with AS were included in this study. Radiographs both at baseline and at the

end of the study were scored using modified the Stoke AS Spine score (mSASSS). A rate of 1≥ unit/year was defined as

radiographic progression. Serum estrogen, dickkopf-1 (DKK1), leptin levels were detected by enzyme-linked im-

munosorbent assay (ELISA) at specific times. Blood samples of 31 patients were assessed by flow cytometry to detect fre-

quencies of Th1, Th2 and Th17 cells. Body mass index (BMI) and other clinical and laboratory characteristics were retro-

spectively collected.

Results: The mean age was 38.8±11.3 years old, and 17 (16.7%) patients were female. In the univariable analysis, es-

trogen serum level (OR 1.01, 95% CI 1.00 to 1.03, p=0.026), BMI (OR 1.35, 95% CI 1.15 to 1.59, p<0.001), initial

mSASSS (OR 1.11 95% CI 1.05 to 1.18, p<0.001), CRP (OR 1.16, 95% CI 1.02 to 1.31, p=0.026), DKK1 (OR 0.99, 95%

CI 0.99 to 1.00, p=0.045), female (OR 0.21, 95% CI 0.04 to 0.98, p=0.047) and disease duration (OR 1.01, 95% CI 1.00

to 1.02, p=0.013) were associated with radiographic progression. In the multivariable analysis, estrogen, BMI, DKK1 and

CRP were associated radiographic progression. In the flow cytometry, frequency of Th17 was significantly increased in

progressors compared with non-progressors (2.7±1.9 vs. 1.0±0.9%, p=0.041). Estrogen level was positively correlated

with the frequency of Th1 and Th17 (r=0.55, p=0.001 and r=0.38, p=0.036, respectively).

Conclusions: Estrogen is associated with radiographic spinal progression in AS patients. Further study is warranted

to clarify the role of estrogen in the pathogenesis of AS.

Poster 59


S238

Severe Bone Marrow Edema on Sacroiliac Joint MRI Increases the Risk of Low BMD in Patients with Axial Spondyloarthritis

Ha Neul Kim1, Joon-Yong Jung2, Yeon Sik Hong1,3, Sung-Hwan Park1, Kwi Young Kang1,3

1Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, 2Department of Radiology, College of Medicine, The Catholic University of Korea, Seoul, 3Division of Rheumatology,

Department of Internal Medicine, Incheon St. Mary's Hospital, The Catholic University of Korea, Incheon, Korea

Background: Patients with axSpA have an increased risk of low bone mass. A recent study showed that nr-axSpA pa-

tients show significantly greater bone loss than patients with mechanical back pain.

Objective: To determine the association between inflammatory and structural lesions on sacroiliac joint (SIJ) MRI and

bone mineral density (BMD) and to identify risk factors for low BMD in patients with axial spondyloarthritis (axSpA).

Methods: Seventy-six patients who fulfilled the ASAS axSpA criteria were enrolled. All underwent SIJ MRI and BMD

measurement at the lumbar spine, femoral neck, and total hip. Inflammatory and structural lesions on SIJ MRI were scor-

ed using the SPondyloArthritis Research Consortium of Canada method. Laboratory tests and assessment of radio-

graphic and disease activity were performed at the time of MRI. The association between SIJ MRI findings and BMD was

evaluated. Multivariate logistic regression analysis identified predictors of low BMD.

Results: Among the 76 patients, 14 (18%) had low BMD. Patients with low BMD showed significantly higher bone

marrow edema (BME) and deep BME scores on MRI than those with normal BMD (p<0.047 and 0.007, respectively).

Inflammatory lesions on SIJ MRI correlated with BMD at the femoral neck and total hip. There was no association be-

tween structural lesions and BMD. The deep BME score correlated with expression of bone resorption markers

(p=0.009). Multivariate analysis identified the presence of deep BME on SIJ MRI, increased CRP, and sacroiliitis on X-ray

as risk factors for low BMD (OR: 5.6, 14.6, and 2.5, respectively).

Conclusion: Acute inflammatory lesions on SIJ MRI were associated with low BMD. The presence of deep BME on SIJ

MRI, increased CRP levels, and severity of sacroiliitis on X-ray were independent risk factors for low BMD.

Poster 60


S239

A20 Expression and Bone Remodeling in Ankylosing Spondylitis

Min Kyung Lee, Hee Jung Ryu, Mi Ryoung Seo, Hyo Jin Choi, Han Joo Baek

Department of Rheumatology, Gachon University Gil Medical Center, Incheon, Korea

Background: A20, an inhibitor of TNF-a-induced apoptosis, has been reported the associations with inflammation by

inhibition of NF-κB activation. And recently A20 deficient mice showed to develop ankylosing spondylitis (AS) and en-

thesitis and A20 was reported to be appeared important in the control of bone resorption in LPS-generated osteoclast.

We investigated the expression of A20 and its correlation with the bone remodeling markers and mSASSS in AS.

Methods: Nine-teen AS patients and 19 healthy controls were enrolled and the expressions of A20 in their PBMCs were

measured by quantitative RT-PCR. The level of Dickkopf-1(Dkk-1) and osteoprotegerin (OPG) as bone remodeling

markers were measured by ELISA. ESR, CRP and mSASSS were checked. Mann Whitney U-test for the comparison of the

expression of A20 and the levels of bone remodeling markers between both group and Spearman analysis for the correla-

tions between the expression of A20 and the level of bone remodeling markers, mSASSS, ESR and CRP were used.

Results: The expression of A20 significantly decreased in AS patients (mean±SEM, 0.44±0.11) compared with in

healthy controls (1.90±0.52, p=0.0026). The mean of mSASSS was 5.63±1.63 and there did not find any correlation

with A20 expression. Dkk-1 and OPG levels in AS patients were not different from in healthy controls. A20 expression

tended to be positively correlated with Dkk-1 in AS patients (r=0.527). OPG levels in AS was not correlated with A20

expression.

Conclusion: The patients with AS showed a significant decreased A20 expression. The deficiency of A20 in AS also

showed the tendency of correlation with decreased Dkk-1, even if it was not statistically significant. This suggests that

the deficiency of A20 might be associated with the pathogenesis of AS and bone remodeling related with Dkk-1 in AS.

Poster 61


S240

Phlegmonous Gastritis in Ankylosing Spondylitis

Bo Young Kim, Shin Ok Jeong, Yoon-Ho Cho, Hyun-sook Kim

Department of Internal medicine, Division of Rheumatology, Soonchunhyang university college of medicine, Seoul, Korea

Phlegmonous gastritis is a rare, rapidly progressive, and potentially fatal bacterial infection. However, because of the

rarity of this disease, the diagnosis and choice of appropriate treatment is difficult. Predisposing factors recognized are

mucosal injury, achlorhydria, and an immunocompromised state. A fifty one-year old man, with a 2-year history of

Ankylosing spondylitis was brought to the emergency room. He presented with nausea and vomiting. Upon examination,

the bowel sounds were hypoactive, the diffuse abdomen was tender to palpation. His blood pressure was 130/80 mmHg,

his heart beat was 88 beats per minute, and his body temperature 37.5oC. He was treated with infliximab from July 2015

to January 2016 and received the treatment in the last two weeks before. The patient underwent aggressive fluid re-

suscitation and was administered prophylactic broad-spectrum antibiotics. He was to keep fasting state. A characteristic

feature of Phlegmonous gastritis is the thickening of the gastric wall on cut section, most marked in the submucosa.

Compared with a computed tomographic (CT) scanning performed one month ago, CT revealed diffuse edematous wall

thickening in entire stomach. In contrast, there was no other specific findings in the colon. One week later, the patient

underwent an esophagogastroduodenoscopy (EGD) that showed edematous, reddish, mucosal change and multiple ul-

cerative lesions on the upper body, lower body greater curvature of the stomach. And diffuse ulcerative lesion on the fun-

dus of stomach was also detected. The patient was diagnosed as a phlegmonous gastritis based on CT and endoscopic

findings. EGD was performed again 10 days later, it was confirmed that the improvement of phlegmonous gastritis. After

a few days, he was able to cosume a diet. This is first reported case of phlegmonous gastritis occurred in AS patients who

received treatment with infliximab. Early recognition and aggressive therapy are important for survival.

Poster 62


S241

Hypergammaglobulinemia is an Indicator of Extraglandular Manifestations in Patients with Primary Sjogren’s Syndrome

In Je Kim1, Roo Min Jun2, Jisoo Lee1

1Department of Rheumatology, Ewha Womans University Mokdong Hospital, Seoul, 2Department of Ophthalmology, Ewha Womans University Mokdong Hospital, Seoul, Korea

Background: Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by lymphocytic infiltration of

exocrine glands. The most common serologic finding is hypergammaglobulinemia which contain several autoantibodies.

Objective: To evaluate the clinical significance of hypergammaglobulinemia in patients with primary SS (pSS).

Methods: Medical records of patients with pSS were retrospectively reviewed and patients with concomitant con-

nective tissue disease were excluded. Demographic, clinical, and serological data were evaluated. Disease activity was as-

sessed using the EULAR Sjögren’s Syndrome Patients Reported Index (ESSPRI). Objective measures of dryness included

Schirmer’s test and measurement of salivary gland function. Patients were grouped according to baseline serum im-

munoglobulin G (IgG) levels; normal IgG (≤1600), mild IgG (1600-2000),and high IgG (>2000).

Results: Of 80 patients (75 female) with pSS, the mean age at diagnosis was 48.6±13.4 years, and the median disease

duration was 2.5 (0.1-14) years. Dry eyes and mouth, and glandular swelling were present in 91.3% and 22.5% of pa-

tients, respectively, and extraglandular manifestations were detected in 85% of patients. Of all patients, 28.8%, 31.2%,

and 40% had normal IgG, mild IgG, and high IgG, respectively. Patients with elevated IgG levels were significantly more

likely to have glandular swelling and extraglandular manifestations including anemia and purpura compared to patients

with normal IgG. Rheumatoid factor positivity, mean number of autoantibodies present, and rate of hypo-

complementemia were significantly higher in patients with elevated IgG. Schirmer’s test results, mean ejection fraction

values of salivary gland scan, and mean total ESSPRI scores were not significantly different between 3 groups.

Conclusions: Hypergammaglbulinemia is very common (72.5%) in patients with pSS. Glandular swelling and extra-

glandular manifestations are more prevalent in pSS patients with hypergammaglbulinemia.

Poster 63


S242

Diagnostic Value of Salivary Gland Ultrasonography in Primary Sjögren’s Syndrome

Ji-Won Kim1, Chan Uk Lee1, Ji-Na Kim1, Jung-Kyu Kim2, Hwajeong Lee1, Sung-Hoon Park1, Seong-Kyu Kim1, Jung-Yoon Choe1

1Division of Rheumatology, Department of Internal Medicine, 2Otorhinolaryngology, Catholic University of Daegu School of Medicine, Daegu, Korea

Background: Serologic, histopathological tests and clinical aspects are used in diagnosing primary Sjögren’s Syndrome.

Recently, ultrasonography has introduced as a simple, noninvasive method to detect salivary gland involvement in pri-

mary Sjögren’s Syndrome. Limited data are available for diagnostic value of salivary gland ultrasonography (SGUS) in

Korea.

Objective: The purpose of this study was to evaluate diagnostic value of SGUS in primary Sjögren’s syndrome, com-

pared to minor salivary gland biopsy or other serologic tests.

Methods: Total 62 patients suspected as Sjögren’s syndrome were enrolled in our study. The SGUS was performed, and

parenchymal echogenicity was graded from 0 to 4. Serologic tests and histopathologic findings of minor salivary gland

were collected retrospectively. Diagnostic accuracy of SGUS was determined by receiver operating characteristic (ROC)

curve analysis.

Results: Forty-seven patients of primary Sjögren’s syndrome were diagnosed by American College of Rheumatology

classification criteria of 2012. The remaining 15 patients constituted control group, which included patients of idiopathic

sicca syndrome or secondary Sjögren’s syndrome. Sum of SGUS grades, from 0 to 16, exhibited better diagnostic value

for primary Sjögren’s syndrome than maximal grade of SGUS. The optimal cutoff value for sum of SGUS grades was 8

with 81% of sensitivity and 73% of specificity.

Conclusion: SGUS had lower sensitivity than minor salivary gland biopsy, but specificity was equal to minor salivary

gland biopsy. SGUS can be used as an additional diagnostic method for primary Sjögren’s syndrome.

Keywords: Sjögren’s Syndrome, Ultrasonography, Salivary Glands, Diagnosis

Poster 64


S243

Clinical Characteristics and Treatment outcomes of Patients with Behcet’s Disease with Vascular Involvement

In Young Kim, Yeonghee Eun, Hyemin Jeong, Hyungjin Kim, Jaejoon Lee, Eun-Mi Koh, Duk-kyung Kim, Hoon-Suk Cha

Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

Background: Vascular manifestations have been reported in up to 50% of patients with Behcet’s disease (BD), most

commonly as venous thrombosis, but all types of vessels can be involved.

Objectives: The aim of this study is to investigate characteristics and treatment outcomes of patients with vascular BD.

Methods: A retrospective review was performed on 2,496 patients who visited our center between 2004 and 2014.

Patients who were suspected to have BD and vascular involvement were enrolled.

Results: 83 patients with clinical features of BD and vascular involvement were identified. Although less than half sat-

isfied the classic International Study Group (ISG) criteria, greater proportion fulfilled the International Criteria for BD

(ICBD), and all of the patients satisfied at least “suspected BD” according to the Japanese criteria. 50 patients had arterial

lesions including 34 with aorta involvement. Another 33 patients had venous thrombosis without arterial lesions.

Patients showed a male predominance (87%) and a predilection of young age with the median of 42 years old. The most

prominent type of arterial lesions was aneurysm (80%) with a high frequency of pseudoaneurysms. Among the aorta, the

thoracic aorta was most commonly involved and 18 patients had aortic valve regurgitation. 75 (90%) patients received

glucocorticoids with a median initial dose of prednisolone of 30 mg per day and 68 (82%) received immunosuppressants.

Half of the patients had more than one relapse after stabilization of the first vascular event. During the course, 44 patients

underwent surgery and/or endovascular treatment and 60% of these patients had repeated treatment for the relapse.

These included 31 aortic valve replacement on 13 patients.

Conclusion: Patients with vascular BD showed a predilection of young male with frequent aneurysmal change and

relapse. Further studies into a practical and specialized diagnostic tool for vascular BD and optimal treatment strategies

are required.

Poster 65


S244

Sleep Quality and Behcet’s Disease

Ji Min Lee, Hye-Jin Jeong, Chang-Nam Son, Ji-Min Kim, Sang-Hyon Kim

Division of Rheumatology, Department of Internal Medicine, Keimyung University School of Medicine, Dongsan Medical Center, Daegu, Korea

Background: Behcet's disease is a chronic, systemic vasculitis. Sleep disturbance is one of the most particular concerns

in patients with Behcet’s disease. It has been known that the disease activity of rheumatoid arthritis and ankylosing spon-

dylosis is associated with the sleep quality. However, studies about the sleep quality of patients with Behcet’s disease in

Korean population are limited.

Objectives: The purpose of this study was to find out the effects of sleep quality on Behcet’s disease in Korean

population. We also investigated the relationship between depression, quality of life and the clinical findings of Behcet’s

disease.

Methods: The study was performed by cross-sectional design. Sleep quality was assessed by the Korean version of

Pittsburgh sleep quality index (PSQI). Disease activity of Behcet's disease was evaluated by Behcet's disease current activ-

ity form (BDCAF). Depression was assessed by the Korean version of Beck depression inventory second edition (BDI-2).

Quality of life was assessed by the Korean version of the Leeds Behcet’s Disease Quality of Life Measure (BDQoL).

Results: Among 100 patients, median age was 51 [44.5-56.0] years, median disease duration was 77.5 [24.0-136.0]

months and 31% were male. The frequency of poor sleep quality (PSQI>5) was 67%. Patients with poor sleep quality

tend to have higher BDI-2, BDCAF and pain VAS score (P<0.001, P=0.028, and P=0.011). Female rate was higher, and

BDQoL was lower in poor sleeper group (P=0.004 and P<0.001). Among 7 PSQI components, daytime dysfunction was

higher in patients with high disease activity (P=0.03). Total PSQI score were strongly correlated with BDCAF score,

BDI-2 score, BDQoL score, and pain VAS score (P=0.02, P<0.001, P<0.001, and P<0.001, respectively).

Conclusions: The low sleep quality is associated with disease activity, depression and quality of life in Korean patients

with Behcet’s disease. Better disease control will improve the sleep quality.

Poster 66


S245

Potential Laboratory Markers Associated with Disease Activity in Behcet’s Disease

Yunjung Choi, Won seok Lee, Wan-Hee Yoo*

Department of Internal Medicine, Chonbuk National University Medical School and Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea

Background: Behcet’s disease (BD) is a rare autoimmune disorder of unknown etiology characterized by involving

multi-organ system. Because there is not a specific test which can reflect disease activity, it is challenging to assess disease

activity and determine treatment strategy based on laboratory parameters.

Objectives: To investigate the laboratory markers as an indicator of disease activity and the correlation between these

parameters and clinical manifestations, retrospectively.

Methods: A total of 115 patients diagnosed with BD based on the criteria of the International Study Group for Behcet’s

Syndrome (ICBS) were enrolled. 65 of whom were active and 50 inactive, according to clinical findings. The neutrophil,

lymphocytes, platelet counts, mean platelet volume (MPV), erythrocyte sedimentation rate (ESR), C-reactive protein

(CRP), complement 3 (C3), complement 4 (C4), and lipoprotein (a) were recorded, and the neutrophil to lymphocyte

ratio (NLR), platelet to lymphocyte ratio (PLR) were calculated from these parameters.

Results: NLR, PLR, ESR, and CRP were significantly higher in patients with active BD group compared with inactive

BD group (all p<0.05). C3 and C4 were higher during the active period than during the inactive phase without statistical

significance. NLR significantly positively correlated with C3 (r=0.54, p<0.01) and C4 (r=0.36, p=0.01). Any laboratory

markers were not associated with oral, genital mucosal ulcer, uveitis, gastrointestinal or vascular lesion in BD. Multiple

Logistic regression analysis revealed that NLR to be an independent factor related to BD activity. (OR=1.41, p=0.04).

NLR showed good accuracy for prediction of disease activity, AUC of 0.706 with cutoff value of 2.7 (sensitivity: 47.7%,

specificity: 86.0%).

Conclusions: NLR, PLR, ESR and CRP might be helpful as biomarkers associated with severity of BD. Especially NLR

can be a simple tool with satisfactory power in predicting the disease activity of patients with BD.

Poster 67


S246

Erosive Arthritis Resembling Osteomyelitis in Behcet’s Disease Patient

Jae Hyun Jung, Sung Jae Choi, Gwan Gyu Song, Jong Dae Ji, Young Ho Lee, Jae-Hoon Kim, Young Ho Seo

Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.

Description: A 48-year-old woman, diagnosed with Behcet's disease (BD), visited to the clinic of reccurent both feet

pain persisted for about 2 years. She received corticosteroids, sulfasalazine, colchicine, and non-steroidal anti-in-

flammatory drugs. After about 2.5 years from first visit, her right foot pain was aggravated. Initially we suspected cellulitis

and started levofloxacin, but after 10 days there was no clinical improvement and MRI of the foot suggested osteomyelitis

with myositis. Bone scans revealed active inflammatory lesions in the right tarsal and left ankle joint areas that resembled

septic arthritis with combined osteomyelitis. Her colonoscopy revealed Behcet's colitis and we added azathioprine. Her

right foot pain improved but she developed left ankle pain. The left ankle and foot pain continued and despite to admin-

istration of levofloxacin for 3 weeks. She did not have infectious signs, so we suspected BD-related arthritis rather than

septic arthritis. We doubled the dose of corticosteroids and sulfasalazine. MRI of the left foot showed joint space narrow-

ing at the tibiotalar joint and suspicious bone erosion at the medial tibia that suggested BD-related arthritis with reactive

bone marrow edema rather than infectious arthritis with osteomyelitis. We started treatment with methotrexate, and

ceased azathioprine and sulfasalazine, and her joint symptoms improved.

Conclusions: Behcet’s arthritis should be considered in the differential diagnosis of BD patients with articular manifes-

tations that may be septic arthritis, especially when there is no response to antibiotics and negative culture study. After

septic arthritis is excluded, treatment of BD could improve joint symptoms. The long-term management strategy for

these patients should involve careful assessment of articular consequences and regular follow-up to assess changes, in-

cluding radiographic evidence of joint damage.

Poster 68


S247

Risk Factors for Mortality in ANCA-Associated Vasculitides

Gi Bum Bae*, Jeong Soo Eun, Na Ri Kim, Eon Jeong Nam, Young Mo Kang

Department of Internal Medicine (Rheumatology), Kyungpook National University School of Medicine, Daegu, Korea

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) has a high mortality rate,

although the introduction of cyclophosphamide and corticosteroids has changed the natural history of disease. However,

reported causes of death (COD) and risk factors for mortality vary between studies.

Objectives: To investigate the COD and risk factors for mortality in patients with AAV.

Methods: A retrospective study was conducted in 44 patients with microscopic polyangiitis (MPA) and 12 gran-

ulomatosis with polyangiitis (GPA) from January 1999 to December 2011. We reviewed medical records of patients in-

cluding demographic characteristics, clinical features, treatment agents, and causes of death.

Results: The mortality rate was 41.1% (23/56) with 5 deaths in patients with GPA and 18 with MPA. Among the sig-

nificant risk factors for mortality on univariate analysis, which include diffuse alveolar hemorrhage (DAH), renal involve-

ment, ≥4 organ involvements, ≥2 five factor score, and ≥4 treatment modalities, a multivariate regression analysis iden-

tified DAH as an independent predicting factor (OR, 10.28; 95% CI, 2.58-40.56; p<0.001). In an analysis of COD, nine-

teen deaths (82.6%) were related to infection. The most common COD was pneumonia (73.9%) which, in turn, was asso-

ciated with DAH (OR, 27.18; 95% CI, 4.30-171.80; p<0.001) and ≥4 organ involvement (OR, 7.62; 95% CI, 1.54-37.71;

p=0.013) as independent risk factors. Bacteria were the most frequent microorganisms causing pneumonia (68.2%), fol-

lowed by fungi (12.7%) and Pneumocyctis jirovecii (11.1%). Most frequently isolated bacteria were Acinetobacter bau-

manii (6 cases), and Staphylococcus aureus (6 cases). There were no significant difference in the mean number of patho-

gens between patients who survived and dead.

Conclusions: This study implicated that early intervention of pulmonary infection may be critical to increase survival

rates in AAV patients with DAH or severe manifestations.

Poster 69


S248

Clinical Characteristics and Treatment Outcomes of Patients with Large Vessel Vasculitis Including Takayasu Arteritis

In Young Kim, Yeonghee Eun, Hyemin Jeong, Hyungjin Kim, Jaejoon Lee, Eun-Mi Koh, Duk-kyung Kim and Hoon-Suk Cha


Background: Large vessel vasculitis is a disease that affects aorta or its major branches with the two major variant of

Takayasu arteritis (TA) and giant cell arteritis (GCA).

Objectives: This study aimed to investigate clinical features and outcomes of patients with large vessel vasculitis.

Methods: A retrospective review was performed on 2,496 patients who visited our center between 2004 and 2014.

After exclusion of other diseases, patients with primary large vessel vasculitis were further classified by age of onset and

disease activity. Patients whose ages of onset were younger than 50 years or those who had been diagnosed as inactive

disease at any age were classified as “TA” considering the natural course of TA. Patients with symptom onset older than

50 years with active disease were classified as “non-TA”. The term “GCA” was avoided in this study, since it is uncertain

whether non-TA is truly accord with GCA.

Results: 229 TA and 16 non-TA patients were identified. The majorities were females and 90% of TA patients met the

classic ACR criteria. TA patients had more headache and visual disturbance, while non-TA patients had higher frequency

of arthritis and polymyalgia rheumatica. The major locations of lesion were the aorta and primary branches of arch with

no difference between groups. Stenosis were more frequent in TA patients (99% vs. 63%). 94% of non-TA patients re-

ceived glucocorticoids compared to only 37% of TA patients. Immunosuppressant was given to 15% of TA and 50% of

non-TA patients. 50% of TA patients showed chronic inactive disease course, while 70% of non-TA patients showed sus-

tained activity. However, the overall clinical course of patients with initially active TA was not significantly different from

that of non-TA patients.

Conclusion: We reviewed 245 patients with large vessel vasculitis and classified patients into TA vs. non-TA according

to the onset age and disease activity. Further studies for diagnosis, treatment and monitoring are needed.

Poster 70


S249

Clinical Characteristics and Treatment Outcomes of Patients with Chronic Periaortitis

In Young Kim, Yeonghee Eun, Hyemin Jeong, Hyungjin Kim, Jaejoon Lee, Eun-Mi Koh, Duk-kyung Kim and Hoon-Suk Cha


Background: Chronic periaortitis (CP) is characterized by a fibroinflammatory periaortic cuff in image and adven-

titia-predominant fibrosis in histology. CP encompasses idiopathic retroperitoneal fibrosis and inflammatory abdominal

aortic aneurysm (AAA), and recent studies have documented overlap between CP and IgG4-related disease (IgG4-RD).

Objectives: This study aimed to investigate clinical characteristics and treatment outcomes of patients with CP.

Methods: Overall 2,496 patients who visited our center between 2004 and 2014 were screened, and patients compat-

ible with CP were enrolled based on imaging findings for a retrospective review. Patients were further classified into two

subgroups: IgG4-related and non IgG4-related according to the diagnostic criteria for IgG4-RD proposed by a Japanese

study.

Results: A total of 61 CP patients were identified. Patients showed a male predominance (70%) with the median age

of 61 at diagnosis. The abdominal aorta was most commonly involved (84%), and the thoracic aorta was involved in 46%

of patients. Only 2 patients had stenosis of the aorta, while 19 patients had aneurysmal changes. Ureteral obstruction was

found in 30%. 49 (80%) patients received glucocorticoids and 19 (31%) patients received immunosuppressants. 9 pa-

tients underwent surgery including 7 cases of AAA repair, 2 cases of aortic valve replacements and 4 patients underwent

endovascular AAA repair. 60% of patients achieved remission without relapse during the course. When the Japanese cri-

teria for IgG4-RD were applied, 10 patients were classified as IgG4-related and 25 as non IgG4-related. There was no sig-

nificant difference in clinical features, treatment outcomes between groups, with the exception of older age, higher serum

globulin, IgG and IgG4 levels and greater pancreas involvement in IgG4-related patients.

Conclusion: We identified 61 CP patients including ten IgG4-related cases. Further studies for pathogenesis and treat-

ment strategies are warranted.

Poster 71


S250

ANCA is Associated with the Clinical Manifestations of EGPA

Dae-Sik Kim, Jung Yoon Pyo, Se-Jin Byun, Sung Soo Ahn, Jungsik Song, Yong-Beom Park, Soo-Kon Lee, Sang-Won Lee

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea

Background: Eosinophilic granulomatosis with polyangiitis (EGPA), formerly named Churg Strauss syndrome, is clas-

sified among the small and medium-sized vessel vasculitis associated with antineutrophil cytoplasmic antibody (ANCA).

During the course of the disease, various symptoms and inflammatory feature of organ can occur.

Objectives: The objective of this study was to determine the relationship between clinical features and ANCA in EGPA.

Methods: We retrospectively reviewed medical records of thirty patients, who had been first classified as EGFA at

Yonsei University Health System, from January 2010 to December 2014. All patients were categorized according to the

six American College of Rheumatology (ACR) classification criteria.

Results: The median age of 71 SLE patients was 50.3 (37.0-56.0) and the proportion of female gender was 60.0%.

Among the ACR criteria, eosinophilia was the most commonly satisfied factor (86.7%). ANCA was measured in 28 pa-

tients and was positive in fourteen (50.0%) (p-ANCA : 39.3% vs c-ANCA : 10.7%). The most common clinical feature

was asthma (83.3%) followed by sinusitis (76.7%) and pulmonary infiltrates (60.0%). Neuropathy was diagnosed in 17

(56.7%) of the patients, 2 (6.7%) of whom had both peripheral neuropathy and central nervous system manifestations.

ANCA positive patients had significantly more frequent renal and neurologic involvement than ANCA negative patients

(Renal involvement: 6 (43.9%) vs 1 (7.1%), p=0.029, Neurologic involvement: 12 (85.7%) vs 4 (28.6%), p=0.002). In

ANCA negatie patients, Lung infiltrates was more frequent than in ANCA positive, but the differences were not statisti-

cally significant (Fig. 1). Treatment response was not significantly different between ANCA positive and negative (Table 1).

Conclusions: The clinical manifestations of EGPA patients differ according to their ANCA status. ANCA positive pa-

tients showed more frequent renal and neurologic involvement.

Poster 72


S251

Effect of Teriparatide in Patients with Osteoporosis and Rheumatoid Arthritis

Sae Young Lee1*, Robin Dore2, Kenneth Saag3, Guillermo Valenzuela4, Kathleen Taylor5, Qiu He5, Jahangir Alam5, Kelly Krohn5

1Lilly Korea, on behalf of Eli Lilly and Company, Indianapolis, IN, 2University of California, Los Angeles, CA, 3The University of Alabama at Birmingham, Birmingham, AL, 4Integral Rheumatology and Immunology Specialists, Plantation, FL,

5Eli Lilly and Company LLC, Indianapolis, IN, USA

Background: A common complication in rheumatoid arthritis (RA) is osteoporosis (OP) with increased incidence of

fragility fractures.

Objectives: The effect of teriparatide (TPTD) on clinical vertebral (VERT) and nonvertebral (NV) fragility fractures,

BMD and safety was examined in the subgroup of OP patients with RA enrolled in the open-labeq,prospective,ob-

servational DANCE trial.

Methods: Patients were treated with TPTD 20 g/day for ≤2 years and followed for up to 2 more years. Mixed model

repeated measures analysis was used to evaluate BMD changes over 18 months. New clinical VERT or NV fragility frac-

tures after 6-24 mo vs 0-6 mo of TPTD therapy and time to new NV fragility fracture were compared.

Results: Of 4085 patients who received ≥1 dose of TPTD, 544 had documented RA. Patients with vs without RA at

baseline had similar age but significantly more history of prior NV fractures, higher L1-L4 T-scores, more baseline clinical

conditions, more glucocorticoid use. Mean TPTD exposure was similar. Over 18 mo, bone density in the spine, femoral

neck,and total hip increased similarly in patients with vs without RA. Incident rates of new VERT or NV fragility fractures

decreased in mo 6-24 vs mo 0-6. There was no significant difference in the decrease in fracture incidence in mo 6-24 vs

mo 0-6in the patients with vs without RA, regardless of the type of fracture. There was no difference in the time to a new

NV fragility fracture by RA status. NV fracture incidence rates/100 patient-years decreased vs reference baseline during

treatment and stayed down. TPTD was well tolerated overall, and no new significant safety findings were observed.

Conclusion: Patients with RA receiving TPTD showed similar increases in BMD at the spine, femoral neck, and total

hip, and similar reduction in the incidence of NV fractures compared with patients without RA. The incidence of NV frac-

tures remained down after drug cessation.

Poster 73


S252

Effect of Urate Lowering Therapy on Renal Disease Progression in Hyperuricemic Patients with Stage 4 Chronic Kidney Disease

Kwanghoon Lee

Department of Internal Medicine, Dongguk University Ilsan Hospital

Objective: To determine whether urate lowering therapy (ULT) delays renal disease progression in hyperuricemic pa-

tients with stage 4 chronic kidney disease (CKD) and whether the baseline stage of CKD affects renal outcomes in ULT

treatment.

Methods: One hundred and forty three patients (53 treated with ULT and 90 with conventional treatment only) with

both hyperuricemia and stage 4 CKD were retrospectively reviewed. Several renal outcomes including the proportion of

patients with renal disease progression were compared between the 2 groups (Non-ULT vs. ULT). In order to evaluate

the implication of baseline stage of CKD, we combined the data of current study with that of our previous one, which dealt

with patients with stage 3 CKD, and performed binary logistic regression analysis for factors associated with renal disease

progression.

Results: We found no significant difference between the 2 groups in terms of the proportion of patients with renal dis-

ease progression (55/90 (61.1%) vs. 33/53 (62.3%), P=1.000), the proportion of patients who started dialysis (31/90

(34.4%) vs. 23/50 (43.4%), P=0.291) and the mean change of eGFR value from baseline (-8.0±10.0 vs. -8.3±10.4,

P=0.878). Binary logistic regression analysis revealed that baseline stage of CKD (3a, 3b and 4) was independently asso-

ciated with renal disease progression (P for trend<0.001).

Conclusion: ULT did not show any benefit on renal disease progression in hyperuricemic patients with stage 4 CKD.

The effect of ULT decreased as the renal disease progressed.

Poster 74


S253

The Efficacy and Tolerability of Febuxostat in Hyperuricemic Patients Undergoing Dialysis

Doo-Ho Lim1, Ji Seon Oh2, Byeongzu Ghang3, Seokchan Hong3, Yong-Gil Kim3, Chang-Keun Lee3, Seung Won Choi1, Bin Yoo3

1Division of Rheumatology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, 2Division of Rheumatology, National Medical center, Seoul, 3Division of Rheumatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Background: Febuxostat is metabolized mainly in the liver and is excreted through both urine and feces, suggesting

that it may be an alternative choice for the treatment of hyperuricemia and gout in chronic kidney disease (CKD) patients.

However, there are insufficient data on the use of febuxostat in patients undergoing dialysis.

Objectives: The aims of our study were to investigate the efficacy and tolerability of febuxostat in hyperuricemic pa-

tients on dialysis.

Methods: We retrospectively reviewed clinical and laboratory data from two tertiary referral centers from January 2012

to December 2015. We included 49 patients with underlying CKD on dialysis who started febuxostat treatment in the

two hospitals.

Results: The mean age of the study patients was 54.4±12.5 year and follow-up duration was 12.7±10.2 months. Thirty

six patients (73.5%) were also diagnosed with gout. Among 41 patients who were treated with febuxostat for over 3

months, the mean serum uric acid level at 3 months after treatment (4.97±1.84 mg/dL) was significantly reduced com-

pared with the pretreatment level (9.61±2.18 mg/dL) (p<0.001). And the serum uric acid level stayed significantly lower

for 12 months without deterioration in eGFR. Of the 49 patients, only 2 stopped the medication due to adverse event.

The two patients who stopped taking febuxostat were on peritoneal dialysis.

Conclusions: Febuxostat is efficacious and well tolerated in hyperuricemic patients undergoing dialysis. Close ob-

servation for adverse events might be needed for patients on peritoneal dialysis.

Poster 75


S254

Identification of Subclinical Tophi in Patients with Gouty Arthritis: A Dual-energy Computed Tomography Study

In Je Kim1, Ji Young Hwang2, Jisoo Lee1

1Division of Rheumatology, Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, 2Department of Radiology,Ewha Womans University School of Medicine, Seoul, Korea.

Background: Tophi are generally considered as manifestations of chronic gout, but subclinical tophi in intra- and ex-

tra-articular structures have been shown to occur in early gout and asymptomatic hyperuricemia. Since occurrence of to-

phi is linked to joint destruction, it is important to detect tophi early before clinical detection.

Objective: The aim of our study was to evaluate the utility of dual-energy CT (DECT) in detecting subclinical tophi in

patients with gouty arthritis.

Methods: DECT scans of feet in 71 patients with gout without apparent clinical tophi were evaluated for presence of

tophi. Plain X-ray of feet, clinical and laboratory data were obtained simultaneously at the time of the DECT evaluation.

Total volumes of tophi in both feet were quantified using an automated software program of DECT.

Results: The mean age of gout patients was 47.3±14.8 years, and median disease duration was 2.6 (range 0-20) years.

Subclinical tophi were detected in 70 (98.6%) patients and in 793 (39.9%) joints, and median 9 (0 to 26) joints per patient

were positive for tophi. The most common sites for tophi were first metatarsophalangeal joints (17.8%), followed by an-

kle joints (11.0%). Tophi in Achilles tendons were present in 10.8% of patients. Patients with early gout (disease dura-

tion<2 years) had tophi in 99 (13.6%) joints. Mean number and volume of tophi were not significantly different between

early gout and chronic gout.

Conclusions: Tophi frequently occur in both intra- and extra-articular structures of gouty arthritis patients despite ab-

sence of clinically apparent tophi. DECT is an excellent imaging modality for detecting subclinical tophi.

Poster 76


S255

Clinical Features and Risk Factors of Gout Attacks Following Anti-tuberculous Treatment

Sang Wan Chung1, Eun Ha Kang1, Yun Jong Lee1,2, You Jung Ha1

1Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, 2Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea

Background: Taking some anti-tuberculous (TB) drugs is known to induce hyperuricemia and trigger gout attack.

However, there have been no well-described studies for gout during anti-TB therapy.

Objective: The aim of this study was to investigate the clinical features and risk factors of gout attacks following anti-TB

treatment.

Methods: We conducted the case-control study including 20 patients who developed gout attack following anti-TB

medications and 60 age-sex matched TB controls without gout attack. Demographics, clinical features and laboratory

findings of patients with gout attacks following anti-TB therapy were analyzed and compared to those of controls in order

to establish risk factors associated with gout attack during anti-TB treatment.

Results: The mean age was 62.7±15.5 years and 10 patients were male (80%). 11 patients had a previous history of

gout. The mean time interval to develop gout attack was 3.7±5.3 months from the initiation of anti-TB therapy. The at-

tacks tended to involve lower extremity joints (18/20, 90%), especially the ankle joint (10/20, 50%). Patients with gout

attack were treated with rifampin (n=17), isoniazid (n=14), ethambutol (n=14), pyrazinamide (n=10), or others

(n=15). Patients who developed gout following anti-TB medication have higher body mass index (23.8 vs 21.3 kg/m²,

p=0.024), more decreased renal function (eGFR 58.8 vs 83.9 mL/min/1.73m2, p=0.039) and higher pre-treatment se-

rum urate levels (8.3 vs 5.3 mg/dl, p<0.001). An elevated pre-treatment serum urate level was found to be an in-

dependent risk factor for gout attack following anti-TB treatment (OR 2.04, 95% CI 1.32-3.16, p=0.001).

Conclusion: Patients who developed gout attack following anti-TB therapy had higher pre-treatment serum urate level.

We suggest that physicians who start anti-TB therapy in TB patients with high pre-treatment serum urate level should

pay attention to the development of gout attack and educate the patients.

Poster 77


S256

Increased Carotid Intima-media Thickness was Related with Elevated Serum Homocysteine Level

in Patients with Hyperuricemia

Ji Ho Park, Jung-Soo Song, Sang Tae Choi

Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea

Background: Hyperuricemia and hyperhomocysteinemia are known to be associated with metabolic syndrome and car-

diovascular disease. However, there was no report about the relationship between Hcy and atherosclerosis in patients

with hyperuricemia.

Objectives: We investigated whether carotid intima-media thickness (IMT) was increased in patients with

hyperuricemia. We also evaluated the correlation between serum homocysteine (Hcy) level and carotid IMT in hyper-

uricemic patients.

Methods: This study includes 1,228 patients who visited the Health Promotion Center of Chung-Ang University

Hospital from January 2013 to August 2015. Serum Hcy level was measured by a competitive immunoassay using direct

chemiluminescent. Carotid IMT was measured by B-mode carotid ultrasonography. Hyperuricemia and hyper-

homocysteinemia were defined as the serum uric acid>7.0 mg/dL, and as the serum Hcy>15.0μmol/L.

Result: Patients with hyperuricemia showed significantly higher levels in serum Hcy than normouricemic individuals

(13.65±4.47μmol/L vs 11.68±3.65μmol/L, p<0.001). Carotid IMT in hyperuricemia group was significantly thicker

than that in normouricemia group (1.13±0.66 mm vs 1.03±0.53, p=0.029). In patients with hyperuricemia, carotid IMT

was correlated with serum Hcy level (γ=0.209, p=0.007), estimated glomerular filtration rate (eGFR), serum BUN and

Cr levels (γ=-0.318, p<0.001; γ=0.229, p=0.003; γ=0.311, p<0.001, respectively). In multiple linear analyses, car-

otid IMT was affected by eGFR (β=-0.289, p=0.001), however, it was not influenced by glucose level and cholesterol

profiles in patients with hyperuricema.

Conclusions: Carotid IMT was higher in patients with hyperuricemia than in those with normouricemia, and it was

correlated with serum Hcy level in patients with hyperuricemia. This study suggests that decreased renal function in pa-

tients with hyperuricemia leads to elevated serum Hcy level, which in turn leads to atherosclerosis.

Poster 78


S257

Insulin Resistance as an Independent Predictor of Erectile Dysfunction in Patients with Gout

Ji Hun Kim, Howook Jeon, Seo Hwa Kim, Haneul Kim, Jihyung Yoo, Min Kyung Chung, Jung Hee Koh, Jennifer Lee, Ji Yeon Lee, Seung-Ki Kwok, Ji Hyeon Ju, Sung-Hwan Park

Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea

Objectives: Gout is linked with a number of metabolic disorders. Recent studies have reported that erectile dysfunction

(ED) is increased in patients with gout and has been linked with similar comorbidities of gout. The aim of the present

study was to identify independent predictor of ED in patients with gout.

Methods: From August 2014 to August 2015, outpatients who were men and treated for gout in our rheumatology clin-

ic were enrolled. Healthy males without any history of inflammatory disease were included as control group. ED was as-

sessed by using the five-item version of the International Index of Erectile Function questionnaire in participants. Insulin

resistance (IR) was measured by homeostatic model assessment (HOMA). Logistic regression analysis was performed

to estimate the effect of variables on presences of ED on all of the study subjects and patients with gout.

Results: We analyzed 80 patients with gout and 70 healthy controls. The median age of patients with gout was 52 years

and median disease duration was 120 months. Gout patients had more ED compared to controls (55.3% vs. 41.4%,

P<0.047). After adjustment of compounding factors, only HOMA-IR was significantly associated with ED (OR: 1.82,

95% CI: 1.05-3.15). Older age (P<0.001), higher HOMA-IR (P=0.048) and lower glomerular filtration rate (GFR)

(P=0.038) were observed in patients with gout with presence of ED than without ED in gout patients. Multivariate logis-

tic regression analysis showed that HOMA-IR was an independent predictor for the presence of ED (OR: 1.62, 95% CI:

1.03-2.82) in gout patients.

Conclusion: In our study, IR was an independent predictor of ED in patients with gout.

Poster 79


S258

MTHFR C677T Polymorphism is Associated with Increase in Homocysteine but not with Uric Acid

Il Woong Sohn1, Chan-Bum Choi2, Young Seo Kim3, Jae-Bum Jun2

1Department of Rheumatology, Hanil General Hospital, Seoul, 2Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, 3Department of Neurology, Hanyang University Hospital, Seoul, Korea

Background: Hyperhomocysteinemia is reportedly associated with high serum uric acid (sUA) levels. MTHFR C677T

polymorphism is associated with increase in serum homocysteine (sHcy). Some studies have suggested a positive corre-

lation between MTHFR C677T polymorphism and sUA, but it remains unclear.

Objectives: We aimed to evaluate the association between sHcy and sUA as well as MTHFR C677T polymorphism and

sUA.

Methods: Hyperuricemia was defined as >7.0 mg/dl for male and >5.6 mg/dl for female. Hyperhomocysteinemia was

defined as >15μmol/l. Clinical laboratory examinations and genotyping for MTHFR C677T polymorphism was

performed. Statistical analyses were performed using chi-square, Pearson’s correlation coefficients, and ANOVA.

Results: Data from 861 subjects(264 male and 597 female) were analyzed. The mean age was 73.2±11.3 years in male

and 75.3±10.3 years in female. Subjects with elevated sHcy levels had an odds ratio (OR) of 2.7 (95% CI 1.4-5.4) in male

and 2.0 (95% CI 1.4-3.1, p=0.001) in female for hyperuricemia. The genotype frequency of MTHFR C677T was 32.8%

(n=282) for CC, 49.8% (n=429) for CT, and 17.4% (n=150) for TT. TT genotype showed association with hyper-

homocysteinemia when both gender were analyzed (p<0.001, ANOVA). MTHFR C677T polymorphism was not asso-

ciated with sUA level (Table 1).

Conclusion: TT genotype of the MTHFR C677T was associated with hyperhomocysteminema. A positive association

was observed between sHcy levels and sUA levels for both males and females which is in agreement with previous

studies. MTHFR C677T polymorphism is not associated with sUA level, which is inconsistent with recent studies.

Poster 80


S259

Macrophage Migration Inhibitory Factor in Gout

Hae-Rim Kim1, Kyung-Ann Lee1, Kyoung-Woon Kim2, Bo-Mi Kim1,2, Sang-Heon Lee1

1Department of Rheumatology, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, 2Concersant Research Consortium in Immunologic Disease, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea

Objective: Macrophage migration inhibitory factor (MIF) is proinflammatory, angiogenic and tissue degrading

cytokine. This study aimed to determine monosodium urate (MSU)-induced MIF production and the role of MIF in gouty

arthritis.

Methods: Peripheral blood and clinical data were obtained from 98 patients (31 patients with acute gouty arthritis and

67 patients with intercritical gout). Synovial fluid (SF) was obtained from patients with acute gouty arthritis and SF white

blood cells and neutrophils were counted. SF and serum levels of MIF, interleukin (IL)-1, IL-8 and leukotriene B4, were

measure using enzyme-linked immunosorbent assay (ELISA) and their relationship was analyzed. Peripheral blood mon-

onuclear cells (PBMC) were isolated and cultured with MSU crystal, the production of MIF was determined.

Results: SF MIF level was higher in acute gouty arthritis than osteoarthritis. Serum MIF was higher in patients with

intercritical gout than patients with acute gouty arthritis or healthy volunteers. SF MIF level was positively correlated

with SF WBC and neutrophil counts, IL-1β and IL-8 levels in acute gouty arthritis. Serum MIF level was correlated with

IL-1b and IL-8 levels in patients with intercritical gout. MSU crystal induced MIF production in PBMC with maximal ef-

fect at 100 mg/ml.

Conclusion: MIF was highly produced in gouty arthritis and MSU induced MIF production. MIF could be involved in

early inflammatory process in acute gouty arthritis.

Poster 81


S260

A Case of Cryopyrin Associated Periodic Fever Syndrome (CAPS) with Mutation of NLRP3

as Autoinflammatory Syndrome

Sooyeon Lim1, Minji Son1, Yumi Seo1, Kumi Jeong1, Kihwan Kim1, Jungwoo Rhim1, Seungbeom Han1,3, Jinhan Kang1,3, Myungshin Kim2, Daechul Jeong1,3

1Department of Pediatrics, 2Catholic Genetic Laboratory Center, 3Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea

Cryopyrin-associated periodic syndrome(CAPS) is a group of autoinflammatory disorders characterized by mutations

in genes encoding the NLRP3 inflammasome. Affected patients develop episodic fevers, urticaria, and arthralgias. We re-

port a case of CAPS presenting with fevers, rash and arthralgia.

A 13-month-old boy was hospitalized for evaluation of fever and standing difficulty during 1 day. He had urticarial rash

since 1 month after birth, and presented with episodes of prolonged fever. Fever was partially controlled by NSAID and

urticarial rash persisted in spite of anti-histamine and steroid treatment. His physical examination for this admission re-

vealed no significant finding except abnormal skin rash. There was no swelling on any joint and no focus of fever. On labo-

ratory study, there were leukocytosis, high ESR and CRP. Allergy tests including MAST, IgE, and eosinophilic cationic pro-

tein and immunologic tests including serum immunoglobulin were within normal range. Bone scan and auditory brain

response were normal. We evaluated genetic study for CAPS because of uncontrollable fever and persistent urticarial

rash. Gene analysis showed a point mutation on exon 5 (c.932T>C) in NLRP3. There is no serious organ damage like

as neurologic abnormality, hearing loss, joint abnormality or secondary amyloidosis until 13 months of age. Standing and

walking were improved after low dose steroid and NSAID. We must be close observation and monitoring after treatment

with anti-IL1 inhibitor.

Fever with rash is common symptoms due to infection in children. We have to consider autoinflammatory disease in

child with repeated fever and skin manifestations in the absence of definite infections.

Poster 82


S261

Treatment Pattern and Its Cost of Vertebral Fracture among Elderly Patients in Korea

Dam Kim1, Jeonghoon Ahn2, Yoon-Kyoung Sung1

1Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, 2National Evidence-based Healthcare Collaborating Agency, Seoul, Korea

Background: Vertebral fracture (VF) is a hallmark of osteoporosis, and it increases morbidity, mortality and large

amount of medical cost.

Objectives: In this study, we aimed to describe the treatment pattern and estimate the cost of VF among elderly pa-

tients in Korea.

Methods: Using Korean national healthcare claims database, we analyzed a 2% sample of patients aged ≥50 years be-

tween years of 2008 and 2012. New VF was identified on the basis of selected ICD-10 codes in patients who did not have

VF in past 1 year, and medical cost includes in-hospital and outpatient medication cost. After estimating incidence of VF,

treatment pattern and medical cost in first and second year in VF were compared according to age and gender.

Results: The incidence of VF was much higher in female (616 and 1,597 per 100,000 in male and female, respectively).

The 14% of patients underwent vertebroplasty or kyphoplasty, 42% of patients needed hospitalization for pain control,

the other 43% were treated without hospitalization. Patients aged 50-59 years showed lowest proportion for verte-

broplasty or kyphoplasty (1.8% in male and 8.2% in female), the proportion was increased with the age (7.9% in male

and 12.2% in female aged 60-69 years; 16.7% and 17.5% in 70-79 years; 20.0% and 17.7% ≥80 years). Patients under-

went vertebroplasty or kyphoplasty paid the largest medical cost in first year (w1,973×103 in male and w1,950×103 in

female), followed by hospitalization (w981×103 and w885×103) and without hospitalization (w393×103 and

w338×103). In addition, medical cost according to age group did not show significant trend, whereas proportion of medi-

cal cost in second year was increased with age.

Conclusion: In Korean patients with VF, 14% of patients underwent vertebroplasty or kyphoplasty, and the proportion

was increased with age. In addition, older patients tend to pay more medical cost for longer period.

Poster 83


S262

Evaluation of the Inpatient Rheumatology Consultation Service: A Single Tertiary Center Experience

Chan Uk Lee, Sung- Hoon Park, Hwajeong Lee, Ji-Na Kim, Ji-Won Kim, Seong-Kyu Kim, Jung-Yoon Choe

Division of Rheumatology, Department of Internal Medicine Catholic University of Daegu School of Medicine, Korea

Background/Objectives: Consultation is an important aspect of rheumatology fellowship training and an essential

service provided by academic rheumatology divisions. The objective of this investigation is to profile the spectrum of dis-

ease which might be encountered in the consultation service.

Methods: The medical records of all patient consults during the year 2015 at a university hospital were reviewed with

regard to reason for consult, demographic data, and final rheumatologic diagnosis and consequences.

Result: A total of 478 consultations regarding 374 patients were seen on medical center consult service in 2015. Mean

age of patients was 57.7 year-old, and 242 (65%) patients were female. There were 190 patients related rheumatoid dis-

ease and 184 patients not related. Among patients with rheumatic disease, 115 (30.7%) patients were previously diag-

nosed to rheumatic disease and 75 (20.0%) patients were newly diagnosed during hospitalization. The 6 major disease

entities of newly diagnosed patient were crystal arthropathy, systemic lupus erythematous, vasculitis, adult onset still`s

disease, and rheumatoid arthritis. Two main reasons for consultation were laboratory abnormalities (anti-nuclear anti-

body, anti-neutrophil cytoplasmic antibody, anti CCP antibody, rheumatoid factor, etc.) and musculoskeletal symptom

(arthralgia and/or fever), or mixture them. Among patients with newly diagnosed as a rheumatic diseases, 67 (17.9%)

patients were consulted from division of infectious diseases followed by division of cardiology, neurology, and pulmonary

diseases.

Conclusion: There were a significant number of patients newly diagnosed with rheumatic diseases by consultation

service during hospitalization period. We need to be more cautious to patients with an important symptom and sign, es-

pecially arthralgia and/or fever.

Keywords: Consultation, Rheumatology, Hospitalization

Poster 84


S263

Utilization Patterns of Medication in Women with Rheumatoid Arthritis of Childbearing Age:

Result from KORONA Cohort

Soo-Kyung Cho1,2, Yoon-Kyoung Sung1,2, Dam Kim1,2, Soyoung Won2, Hoon-Suk Cha3, Jung-Yoon Choe4, Chan-Bum Choi1,2, Won Tae Chung5, Seung-Jae Hong6, Jae-Bum Jun1, Jinseok Kim7, Tae-Hwan Kim1, Eunmi Koh3,

Hye-Soon Lee8, Jisoo Lee9, Shin-Seok Lee10, Sung Won Lee5, Dae-Hyun Yoo1, Sang-Cheol Bae1,2

1Hanyang University Hospital for Rheumatic Diseases, Seoul, 2Clinical Research Center for Rheumatoid Arthritis (CRCRA), Seoul, 3Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, 4Catholic University of Daegu School of Medicine, Daegu,

5Dong-A University Hospital, Busan, 6Kyung Hee University Hospital, Seoul, 7Jeju National University Hospital, Jeju, 8Hanyang University Guri Hospital, Guri, 9Ewha Womans University Mokdong Hospital, Seoul, 10Chonnam National University Hospital, Gwangju, Korea

Objectives: This study aimed to compare the disease activity between the women RA with childbearing age who were

planning a pregnancy and who were not planning a pregnancy, and identify the difference in their utilization of the medi-

cines for RA.

Methods: We included 1,440 women with RA of childbearing age from the KORONA cohort. The patients were catego-

rized into those with a pregnancy plan (n=596) and without a pregnancy plan (n=844). The disease activity calculated

by disease activity score 28 ESR (DAS28ESR) and the patterns of DMARDs, and corticosteroids use were compared be-

tween two groups using the Chi-square test.

Result: The women patients with a pregnancy plan had significantly lower age at 37.3 compared to those without a

pregnancy plan at 43.2 (p<0.001). The DAS28 ESR was similar between two groups (3.65±1.33 for the patients with

a pregnancy plan vs. 3.60±1.32 for the patients without a pregnancy plan, p=0.51). The proportion of the patients with

remission was higher in patients with a pregnancy plan at 25.0% than at 23.3% in patients without a pregnancy plan, but

there was not statistically significant (p=0.38). In the utilization of medication, the methotrexate and leflunomide use

were lower in the patients with a pregnancy plan than those of the patients without a pregnancy plan (80.0 % vs. 87.3%,

p<0.001 in methotrexate, 26.5% vs. 33.7% in leflunomide, p=0.005). On the other hand, the corticosteroid and biologic

DMARDs use were higher in the patients with a pregnancy plan than those of the patients without a pregnancy plan

(74.0% vs. 68.8%, p=0.04 in corticosteroid, 8.7% vs. 4.5%, p=0.002 in biologic DMARDs).

Conclusion: The disease activity of the women RA with childbearing age who had pregnancy plan was similar to that

of the patients without a pregnancy plan. In the use of medicine, the patients with pregnancy plan used less methotrexate

and leflunomide and more corticosteroid and biologic DMARDs compared to the patients without pregnancy plan.

Poster 85


S264

The Effect of Rheumatoid Factor on All-cause, Cardiovascular and Cancer-cause Mortality in 296,581 Korean Subjects:

A Kangbuk Samsung Health Study

Joong Kyong Ahn1, Jiwon Hwnag2, Seungho Ryu3, Yoosoo Chang3

1Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, 2Division of Rheumatology, Department of Internal Medicine, National Police Hospital, Seoul, 3Department of Occupational and

Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea

Background: The presence of rheumatoid factor (RF) in patients with rheumatoid arthritis (RA) associates with an in-

creased overall mortality. However, the clinical effect of RF are incompletely known, particularly in general populations.

Objective: The aim of this study was to determine the association of RF with mortality due to all-causes, cardiovascular

disease (CVD), and cancer in Koreans.

Methods: Among 295,581 participants of a health-screening program between 2002 and 2012, the risk of death from

all-causes, CVD, and cancer was calculated based on the presence or titers of RF. Vital status and confirmation of the

cause of death were based on the analysis of death certificate records from the National Death Index.

Results: The prevalence rate of RF positivity (RF>20 IU/L) was 4.4 %. During 1,449,464.9 person-years of follow-up,

1,404 participants died. The mortality risk due to all-cause and cancer-cause significantly increased in RF-positive sub-

jects compared to RF-negative subjects, respectively (HR 1.34, 95% CI 1.12-1.61; HR 1.35, 95% CI 1.05-1.74). All-cause

mortality risk significantly increased about two-fold in subjects in the 2nd quartile (20-49 IU/mL) compared with

RF-negative subjects after adjusting confounding factors (HR 1.96, 95% CI 1.38-2.78). The HR for cancer-cause mortal-

ity linearly increased as RF increased. In particular, cancer-cause mortality risk significantly increased in subjects with RF

>100 IU/L (HR 2.04, 95% CI 1.29-3.21). However, the HR for cardiovascular mortality was not higher in RF-positive

subjects than RF-negative subjects (HR 0.94, 95% CI 0.52-1.71).

Conclusions: Mortality risk from all-causes and cancer significantly increased in RF-positive subjects compared with

RF-negative subjects. The HR for cancer-cause mortality linearly increased depending on RF titer.

Poster 86


S265

Prevalence and Incidence of RA and Medical Care Utilization in Elderly Onset RA Patients:

An analysis of Korean National Health Insurance Claims Data

Soyoung Won1, Soo-Kyoung Cho1,2, Dam Kim1,2, Minkyung Han1, Jiyoung Lee1, Hyuk Hee Kwon2, Eun Jin Jang3, Yoon-Kyoung Sung2, Sang-Cheol Bae1,2

1Clinical Research Center for Rheumatoid Arthritis (CRCRA), Seoul, 2Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, 3Department of Information Statistics, Andong National University, Andong, Korea

Objects: To identify the prevalence and incidence rates of RA and to investigate the pattern of medical care and drug

utilization in Korea.

Methods: We used Korean National Health Insurance claims data. In 2009-2012, RA was defined by having a medical

claim with RA, prescription of DMARDs within one year after the claim. RA patients identified in 2010 claims with no

codes or prescription for RA during the previous one year and continuous treatment for RA in 2011-2013 were defined

as the incident cases in 2010, and classified into 2 groups: elderly onset RA patients (EORA, ≥60 years) and young onset

RA patients (YORA, ≥19 and <60 years). The patterns of medical care and drug utilization were compared.

Results: The prevalence of RA increased every year (0.28 to 0.32%), and the incidence of RA was 28 per 100,000 per-

son-years. Among the prevalent cases, the use of biologic DMARDs increased (2.3 to 4.1%). Hydroxychloroquine (HCQ)

(57.5-62.5%) was most commonly used non-biologic DMARDs, followed by methotrexate (MTX) (50.0-51.9%). The use

of leflunomide (15.2 to 18.5%) and taclorimus (1.5 to 4.4%) increased, while use of HCQ (62.5 to 57.5%) and sulfasala-

zine (SSZ) (25.5 to 22.4%) decreased. The number of outpatient visit (14.5 vs 13.8) and the frequency of hospitalization

with RA code (18.8 vs 11.3%) were higher in EORA. Use of biologic DMARDs (1.4 vs 2.4%) was less frequently, while

NSAIDs (98.2 vs 97.7%) was used more frequently in EORA than YORA. Use of any non-biologic DMARDs was similar

between the 2 groups. HCQ was more frequently used in EORA (75.0 vs 72.1%), but MTX (55.2 vs 59.3%) and SSZ (28.0

vs 32.7%) were used less frequently than YORA.

Conclusions: Prevalence of RA is in increase in Korea. Use of medical care utilization was higher in EORA. The use

of biologic DMARDs were low in both groups and EORA receiving even less biologic DMARDs than YORA. The use of

non-biologic DMARDs similar between 2 groups, but EORA used more HCQ and less MTX and SSZ than YORA.

Poster 87


S266

Medical Care Utilization among the Korean Patients with Systemic Lupus Erythematosus

Seung Lee1, Young Bin Joo1, So-Yeon Park2, Hyuk Hee Kwon1, Hye-soon Lee1, Yoon-Kyoung Sung1, Sang-Cheol Bae1

1Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, 2Department of Rheumatology, Myongii Hospital, Goyang, Korea

Background: This study aimed to investigate the medical utilization in SLE patients using Korean National Health

Insurance (NHI) claims database covering almost all Korean population.

Methods: The distribution of the number of patients who used medical care were evaluated according to the type of

medical service, medical institutions, specialty of doctors and medications among the prevalent SLE patients between

January and December in 2010.

Results: The prevalent SLE patients in 2010 were 13,047 and their rate per 100,000 was 26.5(95% CI 26.0-27.0). Mean

age was 39.7±14.6 years and female was 85.7%. As investigated the type of medical service, 84.8% of the patients had

outpatient visits with mean visit frequencies of 9.7. 39.2% of the patients had one or more than hospitalization service

with mean hospitalization duration of 14.9 days. 15.7% of patients visited an emergency room and 8.7% of patents under-

went surgery. In the type of medical institution, tertiary hospital was the most commonly visited institution (67.0%), fol-

lowed by general hospital (20.9%), community hospitals/clinics (11.5%). Disease of the connective tissue (79.9%), pep-

tic ulcer (29.6%)and chronic lung disease (25.5%)were the top three common causes of visits. The most frequent spe-

cialty of prescribing doctor was internal medicine (80.8%, the proportion of rheumatology was 72.2% within internal

medicine), followed by orthopedics (6.8%), pediatrics (2.9%). The percentage of prescribed medication was cortico-

steroids (72.9%), anti-malarial agents (64.2%) and immunosuppressants (34.4%).

Conclusion: About 88% of SLE patients have used large teaching (tertiary or general) hospitals and only 11.5% of them

have used small hospital/clinics. Rheumatologists were responsible for about 58% of patients with SLE.

Poster 88


S267

A Case of Serotonin Syndrome Following the Administration of Duloxetine in a Fibromyalgia Patient:

Case Report and Review of Literature

Joon Sul Choi, Ji Hyun Lee

Division of Rheumatology, Department of Internal Medicine, Maryknoll Medical Center, Busan, Korea

Serotonin syndrome is an adverse drug reaction that is a consequence of excess serotonergic agonism of central nerv-

ous system receptors and peripheral serotonergic receptors. Large numbers of drugs and drug combinations have been

associated with the serotonin syndrome, and generally occur in cases that have ingested drugs that synergistically in-

crease synaptic serotonin. These include monoamine oxidase inhibitors, tricyclic antidepressants, selective serotonin re-

uptake inhibitors, opioid analgesics, antibiotics, antiemetics, and herbal products. Serotonin-norepinephrine reuptake

inhibitor-induced serotonin syndrome is reported to be very rare. It is often described as a clinical triad of mental status

changes, autonomic hyperactivity, and neuromuscular abnormalities, but not all of these findings are present in all pa-

tients and signs of excess serotonin range from tremor and diarrhea in mild cases to delirium, neuromuscular rigidity, and

hyperthermia in life-threatening cases. No laboratory test can confirm SS. Diagnosis is made based on the symptoms and

patient’s history, and several diagnostic criteria have been developed. Management involves the removal of the precipitat-

ing drugs, the provision of supportive care, the control of agitation, the administration of 5-HT2A antagonists, the control

of autonomic instability, and the control of hyperthermia. We experienced a rare case of fibromyalgia accompanied by

tremer, hyperreflexia, spontaneous clonus, muscle rigidity and diaphoresis after 10 days of single use of duloxetine 30mg.

Serotonin syndrome occurred by duloxetine has been reported once in Korea, but that case was reported to occur with

the co-administration of fluoxetine. We report here on this case along with a review of the relevant literature.

Poster 89


S268

Pattern Recognition Receptors in Adult Onset Still’s Disease

Hyoun-Ah Kim1, Chang-Hee Suh1, Ju-Yang Jung1, Hasan MD Sayeed3, Ye Won Kim1, Seonghyang Sohn2

Departments of 1Rheumatology, 2Microbiology, 3Biomedical Science, Ajou University School of Medicine, Suwon, Korea

Objective: Several pattern recognition receptors (CD11b, CD11c, CD32, CD206, CD209, and dectin-1) were quanti-

fied in peripheral blood from AOSD patients, rheumatoid arthritis (RA) patients, and HC using cell surface staining and

flow cytometry analysis. The correlations between the frequencies of several pattern recognition receptors and disease

activity were investigated in AOSD patients.

Methods: Thirteen AOSD patients, 19 RA patients as a disease control, and 19 healthy controls (HC) were included

in the study. Follow-up samples were collected form 5 patients after resolution of disease activity.

Results: Significantly higher mean frequencies of surface stained cells presenting CD11b from whole blood were ob-

served in patients with AOSD than in patients with RA and in HC. Also, significantly higher frequencies of surface stained

cells presenting CD32 from whole blood were observed in patients with AOSD than in patients with RA and in HC.

CD11b frequencies from whole cells correlated with systemic score, lactate dehydrogenase (LDH) levels, aspartate trans-

aminase levels, interleukin-23 (IL-23) levels, and IL-18. The frequencies of CD209 from granulocyte correlated positively

with systemic scores, and the levels of ESR, CRP, ferritin, LDH, IL-23, and IL-18. The frequencies of CD206 from whole

blood cells were increased in patients with active AOSD than them with inactive AOSD. The frequencies of CD209 from

whole blood cells were increased in active AOSD patients than inactive AOSD patients.

Conclusion: In conclusion, the CD11b and CD32 circulating cells were higher in patients with AOSD compared to the

RA and HC, and CD11b cells were correlated with several disease activity markers. CD209 circulating granulocytes were

correlated with systemic scores, ESR, CRP, ferritin, LDH, IL-23, and IL-18. Also, the frequencies of CD206 and CD209

from whole blood cells were increased in patients with active AOSD than them with inactive AOSD.

Poster 90


S269

TLR4 Endogenous Ligand S100A8/A9 Levels in Adult-onset Still’s Disease and Their Association with Disease Activity and Clinical Manifestations

Hyoun-Ah Kim1, Jae Ho Han2, Ju-Yang Jung1, You-Sun Kim3, Chang-Hee Suh1

Departments of 1Rheumatology, 2Pathology, and 3Biochemistry and Department of Biomedical Sciences, Ajou University School of Medicine, Suwon, Korea

Objective: S100A8/A9 has been suggested as a biomarker of disease activity in patients with systemic juvenile idio-

pathic arthritis and adult-onset Still’s disease (AOSD). We investigated the clinical significance and the pathogenic role

of this marker in AOSD.

Methods: Serum samples were collected prospectively from 20 active AOSD patients, and 20 healthy controls (HCs).

Furthermore, S100A8/A9 expression levels in biopsy specimens obtained from 26 AOSD patients with skin rashes and

8 AOSD patients with lymphadenopathy were investigated via immunohistochemistry. Peripheral blood mononuclear

cells (PBMCs) from active AOSD and HC were evaluated for interleukin-1β (IL-1β) release and S100A8/A9 cell signals.

Results: S100A8/A9, IL-1β and tumor necrosis factor-α (TNF-α) levels in active AOSD patients were higher than

those of HCs. Serum S100A8/A9 levels correlated with IL-1β, TNF-α, ferritin, and C-reactive protein. The grade of in-

flammatory cells expressing S100A8/A9 ranged from 1 to 3 in skin and lymph node biopsies of active AOSD patients. The

grading and strength of staining of cells positive for S100A8/A9 was more intense in the skin lesions with karyorrhexis,

mucin deposition, and neutrophil infiltration. S100A9 was a strong inducer of IL-1β expression in PBMCs from HCs and

AOSD patients. Like LPS, S100A8/A9 induced phosphorylation of c-jun amino-terminal kinase and p38 in PBMCs, sug-

gesting that S100A8/A9 activates TLR4 signaling pathways.

Conclusions: These data suggest that S100A8/A9 may contribute to the inflammatory response by induction of in-

flammatory cytokines in AOSD, and serve as a clinicopathological marker for the assessment of disease activity in AOSD.

Poster 91


S270

Cytokine Profiles of Korean Patients with Adult Onset Still’s Disease Treated with Tumor Necrosis Factor Inhibitors

Seung Taek Song1, SuMan Kang2, Sung Won Lee2, Seoung Wan Nam2, Dae-Hyun Yoo2

1Cheongju St. Mary's Hospital, Cheongju, 2Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea

Background: Adult onset Still’s disease (AOSD) is a rare inflammatory disorder of unknown etiology. Several studies

have reported that pro-inflammatory cytokines are involved in the pathogenesis of AOSD.

Objectives: To investigate predictors for therapeutic response of biologic drugs in refractory AOSD.

Methods: 22 AOSD patients treated with anti-TNFα agents were recruited from a university hospital for rheumatic

diseases in Korea. The dosages of anti-TNFα (infliximab in 18 patients, etanercept in 4, and adalimumab in 3) were same

as rheumatoid arthritis. Serum cytokines (TNFα, IL-1β, IL-6, IL-8, IL-17α, and INF-γ) and IL-2 receptor α in were ana-

lyzed by multiplex flowcytometry. A good response was defined as decreased modified Pouchot score more than 2 score

compared to initial treatment of anti-TNFα inhibitors. A no response was defined as no decrease of modified Pouchot

score. We used the Wilcoxon signed rank test for continuous variable and Fisher’s exact test for categorical variables.

Results: 6 (27.3%) patients showed good response to anti-TNFα inhibitors and 3 (13.6%) patients showed partial

response. 13 (59.1%) patients did not respond to anti-TNFα inhibitors. At starting time point of anti-TNFα inhibitors,

levels of ferritin, TNFα, IL-1β, IL-6, and IFNγ in no responders (mean±SD 4,142.0±7,128.6 ng/mL, 13.8±24.3 pg/mL,

8.7±16.9 pg/mL, 77.1±157.8, and 69.3±146 pg/mL, respectively) seemed to be higher than in good responders

(566.4±633.0 ng/mL, 6.9±10.5 pg/mL, 2.6±2.9 pg/mL, 16.9±18.7 pg/mL, and 13.2±9.1 pg/mL, respectively), but

without statistically significant differences between the 2 groups. We didn’t raise the dosage of infliximab in no res-

ponders, in whom tocilizumab was used as second biologic therapy.

Conclusion: This study showed that AOSD patients who were refractory to anti-TNFα inhibitors might have distinct

cytokine profiles. Therefore, dosage of anti-TNF agents in AOSD patients might be individualized according to pre-treat-

ment cytokine profiles.

Poster 92


S271

Elevated High Mobility Group B1 Levels in Active Adult-onset Still’s Disease Associated with Systemic Score and Skin Rash

Hyoun-Ah Kim, Ju-Yang Jung, Chang-Hee Suh


Objective: High mobility group box-1 (HMGB1) is a nuclear protein and such prototypical damage-associated molec-

ular patterns mediate the immune response in the noninfectious inflammatory response. Adult-onset Still’s disease

(AOSD) is a systemic inflammatory disorder involved in the dysregulation of innate immunity. We investigated the se-

rum HMGB1 level in patients with AOSD and evaluated its clinical significance.

Method: Blood samples were collected from 40 patients with active AOSD and 40 healthy controls (HC). Of the pa-

tients with AOSD, follow-up samples were collected from 16 patients after a resolutionof AOSD disease activity.

Results: Serum HMGB1 levels in patients with AOSD were higher than those of the HC(10.0±5.85 vs. 5.15±1.79

ng/ml, p<0.001). Serum HMGB1levels were found to be correlated with C-reactive protein (CRP)and the systemic score.

The AOSD patient who had a sore throat showed a higher serum HMGB1 level than those patients who did not, and the

patient with a skin rash had higher levels than the patients without. In addition, the serum HMGB1 levels were decreased

after the resolution of disease activity in the AOSD patients who were followed-up.

Conclusions: The serum HMGB1levels were elevated in AOSD patients compared to the HC, and were correlated with

both CRP and the systemic score. The HMGB1 levels were associated with skin rash and a sore throat in AOSD patients.

After the resolution of disease activity, serum HMGB1 levels were found to have decreased

Poster 93


S272

Unbiased Analysis of Fever Curves in Adult Onset of Still’s Disease

Eun Young Ahn1, Hyun MI Kwon1, Woochang Hwang2, Eun Young Lee1, Eun Bong Lee1, Yeong Wook Song1, Jin Kyun Park1

1Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Seoul, 2Data Science for Knowledge Creation Research Center, Seoul National University, Seoul, Korea

Background: Adult onset of Still’s disease (AOSD) is a systemic inflammatory disease characterized by fever, arthritis,

rash and elevated inflammatory markers. The classical fever of AOSD is intermittent with a quotidian or double-quo-

tidian pattern. However, it remains unclear as to whether the certain fever pattern is associated with specific clinical

manifestations.

Objective: To investigate the association between fever pattern and clinical characteristics in patients with AOSD.

Methods: A total of 70 patients with AOSD who were treated as inpatient at Seoul National University Hospital from

2004 through 2015 were enrolled. Fever curves on days 2, 3 and 4 during were grouped using hierarchical clustering.

Results: Patients were clustered into 2 groups based on the fever curves. The 14 patients in the group 1 had a higher

mean temperature (38.1±0.4oC vs. 37.2±0.5oC, p<0.001) with wider daily variation (2.7±0.9oC vs 1.9±0.7oC,

p<0.001) as compared to 56 patients in the group 2. The group 1 tended to by younger (38.4±14.7 years vs. 46.1±17.6

years, p=0.141). Fever, arthritis, arthralgia and rash did not differ between them. Group 1 had significantly lower Plt

count (198,900±68,000/μl vs. 312,900±156,900/μl, p<0.001), higher LDH (816.6±376.4 IU/L vs. 477.5±327.1

IU/L, p=0.002) and higher mean level of ferritin (27,004.1±48,891.5 ug/mL vs 6,852±10,628.2 ug/mL, p=0.072) as

compared to group 2, whereas WBC, CRP did not differ between them. Group 1 tended to require longer time to a clinical

remission (455.5±850 days vs. 9.4±115.7 days, p=0.137).

Conclusion: The systemic analysis of fever curves reveals the presence of at least 2 distinctive fever patterns associated

with AOSD. Spiking fever with higher daily variation was associated with more higher inflammatory markers and re-

quired longer duration until remission. Thus, fever pattern in AOSD might be a prognostic factor.

Poster 94


S273

Serum Uric Acid is Positively Associated with Pulmonary Function in Korean Health Screening Examinees:

A Cross-Sectional Study

Jiwon Hwang1, Jae-Uk Song2, Joong Kyong Ahn2

1Division of Rheumatology, Department of Internal Medicine, National Police Hospital, Seoul, 2Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea

Background: The double-edged characteristics of SUA and mixed results from previous studies have complicated de-

termination of whether serum uric acid (SUA) plays a pulmonary-protective or pulmonary-destructive role.

Objectives: The aim of this study was to determine whether level of SUA, a potent antioxidant, is linked to pulmonary

function in health screening examinees.

Methods: We performed a cross-sectional study on 69,928 Koreans (30,572 men) without overt medical conditions

who underwent a health examination in 2010.

Results: Percent predicted forced vital capacity (FVC%) and forced expiratory volume in 1 s (FEV1%) were positively

correlated with SUA in both genders (FVC%: r=0.361; FEV1%: r=0.314 in males and FVC%: r=0.413; FEV1%: r=0.382

in females, all P<0.001). When quartiles 2, 3 and 4 were compared to quartile 1 (the reference group, highest quartile)

of FVC% by regression analysis, the adjusted ORs for hyperuricemia in men were 0.876 (95% CI, 0.809-0.949), 0.631

(0.574-0.695), and 0.311 (0.278-0.349), respectively. The adjusted ORs for hyperuricemia when quartiles 2, 3 and 4 were

compared to quartile 1 of FEV1% in men were 0.791 (95% CI, 0.729-0.859), 0.565 (0.513-0.623), and 0.302

(0.270-0.337), respectively (P for trend<0.001). Similarly, the adjusted OR of having hyperuricemia in women decreased

significantly across FEV1% and FVC% quartile groups compared to the reference group (P for trend<0.001).

Conclusion: SUA was positively associated with FVC% and FEV1% in a healthy population, supporting the hypothesis

that hyperuricemia protects against impaired lung function.

Poster 95


S274

Clinical Outcomes and Pathological Characteristics of Orbital IgG4-related Disease versus Orbital

Inflammatory Pseudotumor

Hong Ki Min1, Youn Soo Lee2, Suk Woo Yang3, Jennifer Lee1, Seung-Ki Kwok1, Ji Hyeon Ju1, Wan-Uk Kim1, Sung-Hwan Park1

1Division of Rheumatology, Department of Internal Medicine, School of Medicine, The Catholic University of Korea, Seoul, 2Department of Hospital Pathology, School of Medicine, The Catholic University of Korea, Seoul,

3Department of Ophthalmology, School of Medicine, The Catholic University of Korea, Seoul, Korea

Objective: This study investigated the clinical and pathological features of orbital immunoglobulin G4-related disease

(IgG4-RD). To clarify the features, we compared the clinical characteristics and pathological findings of orbital IgG4-RD

and orbital inflammatory pseudotumor.

Materials and Methods: We retrospectively reviewed the medical records of 103 patients who were initially diagnosed

with orbital inflammatory pseudotumor at our tertiary-care medical center in South Korea between January 2008 and

December 2014. We identified 16 cases in which the diagnosis was based on surgical biopsy and for which data in medical

records were sufficient for analysis. Immunohistochemical staining of pathological specimens for IgG and IgG4 was

performed. The Mann-Whitney U-test, chi-squared test, Fisher’s exact test, Kaplan-Meier curves, and log-rank tests were

used for comparisons.

Results: The orbital IgG4-RD group had more IgG4-positive plasma cells and a higher IgG4/IgG plasma cell ratio than

the orbital inflammatory pseudotumor group. Storiform fibrosis and lacrimal gland involvement were significantly more

frequent in the orbital IgG4-RD group. Dense lymphocyte infiltration, obliterative phlebitis, and bilateral lesions were

more frequent in orbital IgG4-RD, but the differences were not significant. The eosinophil count was significantly higher

in the orbital IgG4-RD group. The recurrence-free rate was lower in the orbital IgG4-RD group (P=0.035).

Conclusion: The location of the lesion (lacrimal gland), bilateral involvement, and storiform fibrosis aid the diagnosis

of orbital IgG4-RD in patients with idiopathic orbital mass-like lesions. In addition, maintenance therapy should be con-

sidered in patients with orbital IgG4-RD to prevent recurrence.

Poster 96


S275

Are High Levels of Serum B2 Mikroglobuline, Independent Inflammatory Markers

from Renal Dysfunction in Geriatric Population?

Suleyman Ozbek, Ertugrul Bayram

Cukurova University College of Medicine, Adana, Turkey

Object: This study was to aim to determine the microglobulin level of serum B2 in geriatric patient population as an

inflammatory marker and to compare with other inflammatory markers in order to determine its effectiveness, reliability

and whether it is brittleness marker or not.

Materials and Methods: In order to evaluate the relationship between inflammation and Serum B2 microglobulin level,

totally 81 participants were attended as 20 patients with rheumatoid arthritis (chronic inflammatory disease), 20 pa-

tients with osteoarthritis (chronic non-inflammatory disease), 22 patients with acute infection and 19 control groups

(healthy individuals). Malignancy, grade 3-4 congestive heart failure, renal disfunction, chronic liver disease, obesity, au-

toimmune disease, antiinflammatory, antibiotic and immunosuppressive drug therapy which affect the inflammatory

markers and people who are except from geriatric population and under 65 years of age could not have attended to this

study.

Symptoms: 29 (35.8 %) men and 52(64.2%) women patients have attended. Average of B2 microglobin level of all

groups have been determined as 3.8±1.3 mg/L (1.24-7.9 mg/L). Significant difference was determined as statistically be-

tween groups and B2 Microglobulin level. B2 microglobulin was determined as high in both acute infection and rheuma-

toid arthritis. According to the quality of CFS and SF36; Score of quality of life is the lowest in acute infections. And in-

creased values have been seen in Rheumatoid arthritis, osteoarthritis and healthy individuals. We have determined in-

directly related between Serum B2 Microglobulin level and quality of life. B2 Microglobulin has positive correlation with

age, CRP, sedime, procalcitonin, WBC, ferritin, HES, IL-6, TNF alpha, CFS. Otherwise, it has negative correlation with

hemoglobin, htc, Fe/TİBC (TSAT), D-vitamine, HDL, albumen and SF-36. In the case of acute infectious, the level of D

vitamine, T.cholesterol, HDL, LDL and TG are decreased.

Poster 97


S276

Coexistent Mixed Connective Tissue Disease and Papillary Thyroid Cancer in a Patient with Primary Biliary Cirrhosis:

A Case Report

Ji-Heh Park, Seung-Geun Lee, Eun-Kyoung Park

Division of Rheumatology, Department of Internal Medicine, Pusan National University Hospital, Korea

Case Description: A 40-year-old woman who was diagnosed with primary biliary cirrhosis (PBC) 5 years ago, visited

our hospital complaining of muscle weakness since 8 months, arthralgia, and skin hardening. On physical examination,

all bilateral proximal interphalangeal joints of hands were swollen and tender. Raynaud’s phenomenon (RP) was accom-

panied by telangiectasia and sclerosis on bilateral fingertips. Laboratory results revealed the increased level of creatine

kinase (CK, 4206.2 U/L) and myoglobin (444.9 ng/mL). Electromyographic findings of the upper and lower limbs were

compatible with the active myopathy and histological examination of specimens obtained from the right tibialis anterior

muscle showed inflammatory myositis. ANA was positive and anti-RNP antibody level was 200 U/mL. Anti-cyclic cit-

rullinated peptide antibody, anti-double-stranded DNA, anti-centromere antibody, anti-Scl-70, and anti-Jo-1 antibody

were absent. Therefore, we confirmed mixed connective tissue disease (MCTD) using Alarcon-Segovia criteria based on

positive anti-RNP antibody, synovitis, sclerosis of skin, RP, and myositis. On thyroid ultrasonography, two thyroid nod-

ules in both lobes were founded and histological examination of needle aspiration biopsy specimens revealed nodular hy-

perplasia and papillary thyroid cancer (PTC) in right and left lobes, respectively. Treatment began with intravenous pulse

methylprednisolone of 500 mg for 3 days, followed by 1 mg/kg/day of prednisolone; azathioprine was administered be-

cause of active myositis. After 6-month treatment with glucocorticoids and azathioprine, CK levels declined to 492 U/L

and muscle strength improved significantly. Then, the patient underwent total thyroidectomy.

Conclusion: This is the first report of coexistent MCTD and PTC in a patient with PBC. This case report highlights the

possible association between MCTD and thyroid cancer and suggests that MCTD, similar to other autoimmune diseases,

is associated with PBC.

Poster 98

pp


Journa l o f R heum atic D iseases

Vol. 23, Suppl. 1, May, 2016

2016년 5월 13일 인쇄 2016년 5월 20일 발행

발행인：송 영 욱 편집인：전 재 범 기획인：차 훈 석

발 행： 대한류마티스학회(우: 04376) 서울특별시 용산구 새창로 213-12한강현대하이엘 803호 Tel: 02-794-2630, Fax: 02-794-2631E-mail: [email protected]: www.rheum.or.kr

편집제작：(주)더 위드인(우: 04208) 서울특별시 마포구 만리재로 93 (공덕동 108-1) 비퍼스B/D 2FTel: 02-6959-5333, Fax: 070-8677-6333E-mail: [email protected]

＜pISSN 2093-940X＞＜eISSN 2233-4718＞

Publisher：Yeong-Wook Song Editor in Chief：Jae-Bum Jun

Published byKorean College of Rheumatology

Office of Executive Secretary803 Hangang Hyundai HYEL, 213-12, Saechang-ro,

Yongsan-gu, Seoul 04376, Korea Tel：82-2-794-2630, Fax：82-2-794-2631 E-mail : [email protected] Homepage : www.rheum.or.kr

이 발표논문집은 2016년도 정부재원(과학기술진흥기금 및 복권기금)으로 한국과학기술단체총연합회의 지원을 받아 발간되었음.

This work was supported by the Korean Federation of Science and

Technology Societies (KOFST) grant funded by the Korean Government.

본 학술대회는 한국내과학연구지원재단의 일부 후원으로 개최하였음.

journal of 매일 고통과 함께 눈을 뜨는 아침도, rheumatic diseases ... ·...

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