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Kidney Int. 2015 May;87(5):1061-73. doi: 10.1038/ki.2014.423. Epub 2015 Feb 4.

Efficacy and safety of eculizumab in atypical hemolytic uremic syndrome from 2-year extensions of phase 2 studies.

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Division of Nephrology and Program in Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Emory University and Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
Department of Hematology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Fort Wayne Medical Oncology and Hematology, Fort Wayne, Indiana, USA.
Alexion Pharmaceuticals, Inc., Cheshire, Connecticut, USA.
Department of Kidney and Pancreas Transplantation, Columbia University Medical Center, New York, New York, USA.
Department of Nephrology, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.
Beatson West Scotland Cancer Centre, Glasgow, UK.
Division of Hematology/Oncology, Weill Cornell Medical College, New York, New York, USA.
Department of Surgery/Transplant Center, Houston Methodist Hospital, Houston, Texas, USA.
Department of Renal Medicine, Newcastle University, Newcastle upon Tyne, UK.
Department of Clinical Science, Intervention and Technology (CLINTEC), H9, Karolinska University Hospital, Stockholm, Sweden.
Department of Nephrology, CHU Hotel Dieu-Nantes, Nantes, France.
Adult Kidney Transplant Unit, Université Paris Descartes & Hôpital Necker, Paris, France.
Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy.
Department of Nephrology, Newcastle University, Newcastle upon Tyne, UK.
Department of Nephrology, Istituto Giannina Gaslini, Genova, Italy.
Department of Pediatric Nephrology, Assistance Publique-Hôpitaux de Paris, Hôpital Robert-Debré, Paris, France.


Atypical hemolytic uremic syndrome (aHUS) is a rare, possibly life-threatening disease characterized by platelet activation, hemolysis and thrombotic microangiopathy (TMA) leading to renal and other end-organ damage. We originally conducted two phase 2 studies (26 weeks and 1 year) evaluating eculizumab, a terminal complement inhibitor, in patients with progressing TMA (trial 1) and those with long duration of aHUS and chronic kidney disease (trial 2). The current analysis assessed outcomes after 2 years (median eculizumab exposure 100 and 114 weeks, respectively). At all scheduled time points, eculizumab inhibited terminal complement activity. In trial 1 with 17 patients, the platelet count was significantly improved from baseline, and hematologic normalization was achieved in 13 patients at week 26, and in 15 patients at both 1 and 2 years. The estimated glomerular filtration rate (eGFR) was significantly improved compared with baseline and year 1. In trial 2 with 20 patients, TMA event-free status was achieved by 16 patients at week 26, 17 patients at year 1, and 19 patients at year 2. Criteria for hematologic normalization were met by 18 patients at each time point. Improvement of 15 ml/min per 1.73 m(2) or more in eGFR was achieved by 1 patient at week 26, 3 patients at 1 year, and 8 patients at 2 years. The mean change in eGFR was not significant compared with baseline, week 26, or year 1. Eculizumab was well tolerated, with no new safety concerns or meningococcal infections. Thus, a 2-year analysis found that the earlier clinical benefits achieved by eculizumab treatment of aHUS were maintained at 2 years of follow-up.

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