Genetic diseases and molecular genetics

Nephrology Dialysis Transplantation 28 (Supplement 1): i309–i321, 2013 doi:10.1093/ndt/gft126 GENETIC DISEASES AND MOLECULAR GENETICS MP034 EFFICACY OF ECULIZUMAB IN ATYPICAL HEMOLYTIC UREMIC SYNDROME (aHUS) PATIENTS WITH OR WITHOUT PRIOR TRANSPLANT Christophe Legendre1, David Cohen2, Yahsou Delmas3, Thorsten Feldkamp4, Denis Fouque5, Richard Furman6, Osama Gaber7, Larry Greenbaum8, Timothy Goodship9, Hermann Haller10, Maria Herthelius11, Maryvonne Hourmant12, Christoph Licht13, Bruno Moulin14, Neil Sheerin9, Antonella Trivelli15, Camille L. Bedrosian16 and Chantal Loirat17 1 Université Paris Descartes, Hôpital Necker Paris France, 2Columbia University Medical Center New York NY United States, 3CHU Pellegrin Bordeaux France, 4 University Duisburg-Essen Essen Germany, 5Hôpital E. Herriot and Université de Lyon Lyon France, 6Weill Cornell Medical College New York NY United States, 7 Methodist Hospital Houston TX United States, 8Emory University School of Medicine Atlanta GA United States, 9Newcastle University Newcastle upon Tyne United Kingdom, 10Hannover Medical school Hannover Germany, 11Karolinska University Hospital Stockholm Sweden, 12CHU Hôtel Dieu-Nantes Nantes France, 13 The Hospital for Sick Children and University of Toronto Toronto ON Canada, 14 Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil Strasbourg France, 15 Istituto G. Gaslini Genova Italy, 16Alexion Pharmaceuticals Inc., Cheshire CT United States, 17Assistance Publique–Hôpitaux de Paris, Hôpital Robert Debré Paris France Introduction and Aims: Post-transplant aHUS recurrence leads to graft failure within 1 yr (year) in 60% of patients ( pts).1 Case reports suggest that eculizumab (Ecu) rescues ongoing complement-mediated thrombotic microangiopathy (TMA) and prevents resulting graft loss in pts with post-transplant aHUS recurrence.2 Methods: Ecu efficacy and safety were evaluated in 2 open-label, single-arm, 26-week phase 2 trials with long-term extensions in aHUS pts age ≥12 yrs. Outcomes in non-transplant (NTP) and prior transplant (TP) aHUS pts with progressing TMA or long disease duration and 2 yrs of ongoing Ecu treatment were analyzed. Results: Ecu improved renal function in NTP and TP (Table). Baseline eGFR was not predictive of eGFR change in any group. Shorter time from aHUS clinical manifestation predicted greater eGFR gain in all groups (P≤0.03). Conclusions: Ecu is effective in preserving renal function in NTP and TP and preventing graft loss in TP due to aHUS. These data support early Ecu treatment to prevent ESRD in NTP and prophylactic treatment in pts undergoing transplant. MP034 MP035 EFFICACY OF ECULIZUMAB IN ATYPICAL HEMOLYTIC UREMIC SYNDROME (aHUS) PATIENTS WITH OR WITHOUT A HISTORY OF DIALYSIS Christophe Legendre1, Sunil Babu2, David Cohen3, Yahsou Delmas4, Richard Furman5, Osama Gaber6, Larry Greenbaum7, Maryvonne Hourmant8, Therese Jungraithmayr9, Yvon Lebranchu10, Magdalena Riedl9, Neil Sheerin11, Camille L. Bedrosian12 and Chantal Loirat13 1 Université Paris Descartes, Hôpital Necker Paris France, 2Fort Wayne Medical Oncology and Hematology Fort Wayne IN United States, 3Columbia University Medical Center New York NY United States, 4CHU Pellegrin Bordeaux France, 5 Weill Cornell Medical College New York NY United States, 6Methodist Hospital Houston TX United States, 7Emory University School of Medicine Atlanta GA United States, 8CHU Hotel Dieu-Nantes Nantes France, 9University of Innsbruck Innsbruck Austria, 10University Hospital, François Rabelais University Tours France, 11Newcastle University Newcastle upon Tyne United Kingdom, 12Alexion Pharmaceuticals Cheshire CT United States, 13Assistance Publique–Hôpitaux de Paris, Hôpital Robert Debré Paris France Introduction and Aims: Eculizumab (Ecu), a terminal complement inhibitor, is the only approved treatment for aHUS, a life-threatening disease characterized by chronic uncontrolled complement activation and systemic thrombotic microangiopathy (TMA). Up to 65% of patients ( pts) develop permanent renal damage, end-stage renal disease (ESRD) or die within 1 year of diagnosis.1 Outcomes in pts with progressing TMA( platelets <150×109/L despite ≥4 plasma exchanges/infusions 1 week [wk] before screening) who received 2 years of ongoing Ecu treatment were analyzed based on baseline dialysis status. Methods: Ecu efficacy and safety were evaluated in an open-label, single-arm, 26-wk phase 2 trial with long-term extension in 17 pts age ≥12 years with progressing TMA. Results: Median Ecu treatment duration was 124 wks and 93 wks for dialysis and nondialysis pts, respectively. Baseline characteristics and Ecu efficacy at 2 years were similar in pts with or without dialysis at baseline (Table). Ecu improved platelet counts and renal function in both pt groups. Four of 5 pts (80%) on dialysis at baseline eliminated dialysis and 1 of 12 pts (8%) not on dialysis at baseline started dialysis at wk 64. Ongoing Ecu was safe and well tolerated in both populations. Conclusions: Ecu inhibited hematologic TMA and improved renal function in both pt groups. These data provide evidence for the benefit of Ecu treatment on renal outcomes in aHUS pts, including those on dialysis, regardless of renal function at the start of treatment. MP035 © The Author 2013. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: Abstracts MP036 Nephrology Dialysis Transplantation LONG-TERM IMPROVEMENTS IN OUTCOMES WITH ECULIZUMAB IN PATIENTS WITH ATYPICAL HAEMOLYTIC URAEMIC SYNDROME AND PROGRESSING TMA Neil Sheerin1, Christophe Legendre2, Larry Greenbaum3, Richard Furman4, David Cohen5, A. Osama Gaber4,6, Camille Bedrosian7 and Chantal Loirat8 1 Newcastle University Newcastle upon Tyne United Kingdom, 2Université Paris Descartes & Hôpital Necker Paris France, 3Emory University Atlanta GA United States, 4Weill Cornell Medical College New York NY United States, 5Columbia University Medical Center New York NY United States, 6Methodist Hospital Houston TX United States, 7Alexion Pharmaceuticals Inc. Cheshire CT United States, 8Hôpital Debré Paris France Introduction and Aims: Atypical haemolytic uraemic syndrome (aHUS) is a chronic condition, characterised by systemic thrombotic microangiopathy (TMA), arising from chronic uncontrolled complement activation. Prognosis is poor: up to 40% of patients ( pts) progress to end-stage renal disease or die during the first clinical manifestation. Here, we report long-term follow up data from a clinical trial of eculizumab (ECU), a terminal complement inhibitor, in pts with aHUS. Methods: Efficacy and safety of ECU were evaluated in an open-label, single-arm, phase 2 trial with a long-term extension that enrolled pts age ≥12 yrs with aHUS and progressing TMA ( platelets <150 × 109/L at screening). Pts were treated with ECU 900 mg/wk for 4 wks, 1200 mg at wk 5 and 1200 mg q2 wks thereafter. The primary endpoint was change in platelet count from basel (...truncated)