J ALLERGY CLIN IMMUNOL

VOLUME 127, NUMBER 2

Abstracts AB15

SATURDAY

43 Differences in Ig Replacement Therapy Dosing in Patients with

Common Variable Immunodeficiency in Europe: Results from theESID Database

B. Gathmann1, N. Mahlaoui2, K. Warnatz1, T. W. Kuijpers3, S. S. Kilic4,

V. Thon5, P. D. Arkwright6, D. Kumararatne7, A. Exley8, M. Borte9, A.

Jones10, B. H. Belohradsky11, U. Baumann12, N. K€ut€ukc€uler13, T. Witte14,

C. Feighery15, P. Wagstr€om16, H. Longhurst17, R. Linde18, H. Ritter-

busch1, E. Farmaki19, A. Sediva20, E. Papadopoulou-Alataki21, Z. Panah-

loo22, B. Grimbacher23; 1Centre of Chronic Immunodeficiency (CCI),

Univ Medical Center Freiburg and Univ of Freiburg, Freiburg,

GERMANY, 2CEREDIH: The French PID study group, Unit�e

d’Immuno-H�ematologie & Rhumatologie p�ediatriques, Hopital Necker-Enfants Malades, Paris, FRANCE, 3Emma Children’s Hospital, Academic

Medical Center (AMC), Amsterdam, NETHERLANDS, 4Uludag Univ

Medical Faculty, Bursa, TURKEY, 5Masaryk Univ Medical Faculty, St.

Anne Univ Hospital, Brno, CZECH REPUBLIC, 6Univ of Manchester,

Manchester, UNITED KINGDOM, 7Cambridge Univ Hospital NHS Trust

(Addenbrooke’s), Cambridge, UNITED KINGDOM, 8Cambridge Univ

Health Partners, Papworth Hospital NHS Foundation Trust, Cambridge,

UNITED KINGDOM, 9Children’s Hospital, Municipal Hospital ’St

Georg’, Academic Teaching Hospital of the Univ of Leipzig, Leipzig,

GERMANY, 10Institute of Child Health/Great Ormond Street Hospital,

London, UNITEDKINGDOM, 11Dr v. Haunersches Kinderspital, Ludwig

Maximilians Univ, Munich, GERMANY, 12Paediatric Pneumology,

Allergology and Neonatology, Hannover Medical School, Hannover,

GERMANY, 13Ege Univ, Faculty of Medicine, Dept of Pediatric Immu-

nology, Bornova, Izmir, TURKEY, 14Department of Clinical Immunology,

Hannover Medical School, Hannover, GERMANY, 15Department of

Immunology, Trinity College Dublin & St. James’ Hospital, Dublin, IRE-

LAND, 16Ryhov County Hospital, Jonkoping, SWEDEN, 17Barts and the

London NHS Trust, London, UNITED KINGDOM, 18J. W. Goethe Univ

Hospital, Immunodeficiency Unit, Department of Pediatrics III, Frankfurt,

GERMANY, 19Pediatric Immunology Referral Center, 1st Dept of

Pediatrics, Aristotle Univ of Thessaloniki, Thessaloniki, GREECE,20Department of Immunology, Univ Hospital Motol, Prague, CZECH RE-

PUBLIC, 21Aristotle Univ of Thessaloniki, Medical School, Fourth De-

partment of Pediatrics, Papageorgiou Hospital, Thessaloniki, GREECE,22Medical Science Department, CSL Behring, Haywards Heath, UNITED

KINGDOM, 23Royal Free Hospital & Univ College London, London,

UNITED KINGDOM.

RATIONALE:Commonvariable immunodeficiency (CVID) is character-

ised by low levels of serum immunoglobulins and increased susceptibility

to infections. Standard therapy for patients is immunoglobulin (Ig)

replacement.

METHODS: In a retrospective analysis by country, we analysed CVID pa-

tients within the ESID Database for Primary Immunodeficiencies. Actual

dosing with intravenous (IVIg) and subcutaneous (SCIg) products was

compared to the recommended dose. We used 600 mg/kgBW/month as

the recommended dose, as this is the midpoint between the recommended

400 and 800 mg/kgBW/month. Results represent the median percentage

difference from this figure for IVIg (n5547 patients), SCIg (n5273) and

total Ig patients (IVIg and/or SCIg route, n5647) for each country.

RESULTS: There was wide regional variation in values for IVIg

(p<0.001), SCIg (p50.004) and total Ig patients (p<0.001). The majority

of countries prescribed doses lower than 600 mg/kgBW/month for IVIg

such as Czech Republic (-46%) and Germany (-43%). The Netherlands

(-5%) and Greece (+5%) showed the least variation. The prescribed doses

for SCIg showed a similar picture, with the lowest doses in Czech Republic

(-64%), Germany (-32%), France (-25%), the UK (-22%) and Sweden

(-16%), whilst dosing levels were slightly higher only in Greece (+8%).

Overall, the variations in dosing were similar with IVIg and SCIg (median:

-22% vs. -26%; p50.02).

CONCLUSIONS:This analysis indicates awide regional variation in dos-

ing of Ig replacement therapy across Europe which requires further inves-

tigation of clinical phenotypes, adjunctive treatments (e.g., antibiotics), Ig

serum levels achieved, and, most importantly, clinical outcomes.

44 Tolerability of Human Immunoglobulin 10% AdministeredSubcutaneously Following Administration of RecombinantHuman Hyaluronidase (rHuPH20) in Primary ImmunodeficiencyDisease (PIDD) Patients

D. Gelmont1, R. L. Wasserman2, I. Melamed3, M. Stein4, A. Rubinstein5,

B. McCoy6, W. Engl6, H. Leibl6, R. I. Schiff1, W. J. Grossman1; 1Baxter

BioScience, Westlake Village, CA, 2DallasAllergyImmunology, Dallas,

TX, 3Immunoe Health Centers, Centennial,, CO, 4Allergy Associates of

the Palm Beaches, North Palm Beach, FL, 5Albert Einstein College of

Medicine and Montefiore Hospital, Bronx, NY, 6Baxter BioScience,

Vienna, AUSTRIA.

RATIONALE: Intravenous (IV) and subcutaneous (SC) routes of immu-

noglobulin (IG) administration have both advantages and disadvantages.

One disadvantage of IGSC therapy is the small volumes that can be admin-

istered subcutaneously, requiring multiple infusion sites and frequent ad-

ministrations. rHuPH20 is a permeation enhancer that increases systemic

absorption of SC infused fluids. This Phase 3 study evaluated the tolerabil-

ity of rHuPH20-enabled 10% IGSC infusions at rates and frequencies

equivalent to IGIV administration in PIDD patients.

METHODS: PIDD patients were injected SC with 75 U of rHuPH20/g

IgG, followed at the same site by IGSC doses equivalent to their previous

IGIV dose and administration schedule. Subsequent IGSC dosing was ad-

justed based on IgG trough levels. An interim analysis of tolerability data

was performed on a subset of 30 subjects.

RESULTS:A total of 486 10% IGSC infusions, with or without rHuPH20,

were all administered without interruption. Mean infusion volume every 4

weeks was 302 mL (30.2 g). The mean maximum infusion rate for a single

site was 227 mL/h, and the mean time to infuse was 2.4hrs. Of the 30 pa-

tients analyzed, 29 reached their previous IV dosing interval, with the vast

majority using a single site. Local adverse events (AEs) occurred in 16% of

infusions. Most treatment-related AEs were mild and localized to the infu-

sion site. The rate of all treatment-related systemic AEs was 8% of the

infusions.

CONCLUSION: The subcutaneous administration of 10% IGSC facili-

tated by rHuPH20 was well tolerated, at infusion intervals and rates com-

parable to the patient’s previous IGIV administration.

45 Efficacy Analysis of Immune Globulin Subcutaneous (Human),10% (IGSC) Administered Intravenously or Subcutaneously inSubjects with Primary Immunodeficiency Diseases (PIDD)

R. I. Schiff1, R. L. Wasserman2, I. Melamed3, M. Stein4, W. Engl5, H.

Leibl5, D. Gelmont1, W. J. Grossman1; 1Baxter BioScience, Westlake Vil-

lage, CA, 2DallasAllergyImmunology, Dallas, TX, 3IMMUNOe, Centen-

nial, CO, 4Allergy Associates of the Palm Beaches, North Palm Beach,

FL, 5Baxter BioScience, Vienna, AUSTRIA.

RATIONALE: To evaluate the efficacy of a new IGSC 10% preparation in

terms of rate of infections and protective specific antibody titers.

METHODS: A multi-center, prospective, open label study evaluated effi-

cacy, tolerability and pharmacokinetics of IGSC, 10% given IVor SC to 49

PIDD subjects. Efficacy was determined as the number of acute serious

bacterial infections (ASBI) per subject year, and the overall incidence of

infections and protective specific antibody titers.

RESULTS: The rate of ASBI was 0.067 per subject per year, with an upper

confidence limit of 0.134, well below the established limit of 1 ASBI per

subject per year. There were 3 episodes of acute serious bacterial pneumo-

nia, none of which required hospitalization. The annualized rate of all in-

fections during SC phase of the study was 4.1 infections/subject (95% CI

3.2-5.1). SC infusions were distributed almost evenly over the seasons.

Trough levels of specific antibody to H. Influenza, Hepatitis B surface an-

tigen and tetanus were in the protective range for all subjects during both

IV and SC therapy, with titers substantially higher during the SC phase of

the study for all three specific antibodies.

CONCLUSIONS: Efficacy of IGSC 10% replacement therapy was con-

firmed by rates of infection which are comparable to other SCIG and

IVIG products. These data support application for approval of IGSC

10% as a therapy for patients with PIDD.