10 ani de contribu ie la cercetarea muticentric interna ional în ... bara- ae -new... · ca...
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10 ani de contribu ie la cercetarea muticentric interna ional în
angioedemul ereditar
Dumitru MOLDOVAN
Noémi-Anna BARA
Enik MIHÁLY
Re eaua Român de Angioedem Ereditar
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olilor Ra
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Angioedemul ereditar (AEE)
• boal genetic rar , debilitant i cu poten ial letal
• cauzat de deficien a de C1-inhibitor esteraz (C1-INH)
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Prevalen a
• în lume: 1/10.000 - 1/50.000 de locuitori
• Europa: estimativ 10.000 - 50.000 persoane
• România: estimativ 400 – 2000 persoane
• centrul nostru: 92 pacien i confirma iCon
ferinta Z
iua Bolilo
r Rare 2
017
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Manifest ri clinice
Episoade recurente de edem: - subcutanat localizat- al mucoasei c ilor respiratorii- al tubului gastrointestinal
•Edemul: spontan, nepruriginos, necompresibil, f urticarie
•durat : 3-5 zileCon
ferinta Z
iua Bolilo
r Rare 2
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Manifest ri clinice
• 50% apar pân la vârsta de 10 ani,
• 35% între 10-20 ani i
• 15% peste vârsta de 20 aniConferin
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Atacul periferic (cutanat)• cel mai frecvent, durere
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Atacul abdominal• durere colicativ , gre uri, v rs turi, diaree,
deshidratare• dureaz aproximativ 3 zile• frecvent interven ii chirurgicale inutile interpretate
ca abdomen acut chirurgical
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ta Ziua B
olilor Ra
re 2017
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Atacul facial• cel mai deranjant• desfigurare temporar• 30% edem glotic i risc de
asfixiere
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ta Ziua B
olilor Ra
re 2017
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Atacul laringian• cel mai periculos, 30% risc de deces• de obicei dup vîrsta de 11 ani, mai frecvent la 21-
40 ani• uneori progres rapid (deces în 20 min de la debut)• necesit tratament prompt
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ta Ziua B
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Diagnostic
• Anamnez familial pozitiv în 75% din cazuri
• Simptome caracteristice
• Laborator: C1 esteraz protein i activitate, C4 (în tipurile 1 i 2 sc zute), examen genetic pentru tipul 3.
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olilor Ra
re 2017
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Consensul tratamentului AEE• tratamentul atacului,• profilaxie de scurt durat i • profilaxie de lung durat
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Tratament disponbil în AEE
• plasm proasp t congelat (PPC)• androgenii atenua i (AA): Danazol, Stanozolol,
Oxandrolone • antifibrinolitice(AF): Acid tranexamic(AT), Acid
epsilon amino caproic (AEAC)• concentrat de C1-INH: derivat din plasm
(Berinert, Cinryze, Cetor) i recombinat (Ruconest)
• inhibitor de kallikrein : Ecallantide• antagonist de receptor de bradikinin : Icatibant
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ta Ziua B
olilor Ra
re 2017
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BEHRING CE1145-3001A Randomized, double-blind, 3-arm, placebo-controlled trial to
evaluate human pasteurized C-1 esteraze inhibitor concentrate in subjects with congenital C1-INH deficiency and acute abdominal
or facial HAE attacks. (CE1145).
12 screened patients (*)4 enrolled patients: 3 abdominal and one facial attack(s)Ranked high en-roller (3rd outside US)
2006-2007
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2007-2009
PHARMING 1304A randomized, placebo-controlled, double-blind Phase III study of the efficacy and safety of recombinant human C1 inhibitor for the treatment of acute attacks in patients with
hereditary angioedema
32 screened patients (*)DBPC 2 patients
OLE enrolled 14 patientsOLE treated attacks (safety) 86Patients with 26, 18 and 10 respectively attacks
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ta Ziua B
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2009
PHARMING C1-1207-2009 An Open-label exploratory Phase II study of the safety and Prophylactic Effect of a weekly 50 U/kg rC1INH
treatment in Asymptomatic patients with hereditary C1INH deficiency (HAE).(OPERA)
10 screened and treated patients (*)
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ta Ziua B
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13 screened patients DBPC 5 patientsOLE 110 attacks treatment
2010-2011HGT-FIR-054 A Phase III Randomized Double-blind, Placebo-controlled Multicenter Study of Icatibant for Subcutaneous Injections in Patients with Acute Attacks of Hereditary Angioedema (HAE)
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ta Ziua B
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2011-2013
PHARMING 1310A Phase III randomized, double-blind, placebocontrolled
study with an open-label extension evaluating the efficacy, safety and immunogenicity of recombinant human C1 inhibitor for the treatment of acute attacks of angioedema in patients with HAE
12 screened patients DBPC 9 patientsOLE 100 attacks treatment
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Death and TaxesMeet Joe Black -- Brad Pitt and Anthony Hopkins
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No action indicated (NAI)
September 9-13 2013
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2012-2016
BEHRING CE1145-4001Prospective open-label uncontrolled multi-center postmarketing study to assess inhibitory antibody formation in subjects with congenital C1-INH deficiency and acute hereditary angioedema (HAE) attacks treated with Berinert®, a C1-esterase inhibitor
15 screened patients Enrolled 15 patients138 attacks treatment
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ta Ziua B
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6. Pharming 1209
Safety of Ruconest in 2-13 year old HAE Patients 2 pacienti screenati
2011-2017
2 patients
PHARMING C 1209Open-label, phase II, single arm study to evaluate the safety,immunogenicity, pharmacokinetics and efficacy of recombinanthuman C1 inhibitor for the treatment of acute attacks in pediatricpatients with hereditary angioedema, from 2 up to and including 13years of age
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ta Ziua B
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9.Pharming C1-3201.Phase 2 Multicenter, Randomized, Double-Blind, Placebo-Controlled, 3-Period Crossover to Evaluate the Efficacy and Safety of Recombinant Human C1 Inhibitor in the Prophylaxis of Angioedema Attacks in Patients with Hereditary Angioedema (HAE).Pacienti screnati si randomizati 6
A Phase 3, Multicenter, Randomized, Single-blind, Dose-ranging, Crossover Study to Evaluate the
Safety and Efficacy of Intravenous Administration of CINRYZE® (C1 esterase inhibitor [human] for the
Prevention of Angioedema Attacks in Children 6 to 11 Years of age With Hereditary Angioedema
2015-2016
pacient
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ta Ziua B
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Pharming C1-3201.Phase 2 Multicenter, Randomized, Double-Blind, Placebo-Controlled, 3-Period Crossover to Evaluate the Efficacy and Safety of Recombinant Human C1 Inhibitor in the Prophylaxis of Angioedema Attacks in Patients with Hereditary Angioedema (HAE).
2014-2015
patients
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Shire ViroPharma, IncProtocol: SHP616-300
A huge THANK YOU shout-out goes to all investigators, study coordinators, study staff, and patients from Canada, Germany, Hungary, Israel, Romania, Spain and United States.
Congratulations to the high enrollers for the study:
Dr. Moldovan in Europe (8 Subjects)
Dr. Lumry in North America (7 Subjects),
Dr. Reshef in Middle East (6 Subjects
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În loc de concluzii
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Mul umiri
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Our patients
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MUL UMESC
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