title: Efficacy and safety of eculizumab in atypical hemolytic uremic syndrome from 2-year extensions of phase 2 studies.
abstract: 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.
authors: Division of Nephrology and Program in Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors: Christoph
authors: C
authors: Licht
authors: Emory University and Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
authors: Larry A
authors: LA
authors: Greenbaum
authors: Department of Hematology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors: Petra
authors: P
authors: Muus
authors: Fort Wayne Medical Oncology and Hematology, Fort Wayne, Indiana, USA.
authors: Sunil
authors: S
authors: Babu
authors: Alexion Pharmaceuticals, Inc., Cheshire, Connecticut, USA.
authors: Camille L
authors: CL
authors: Bedrosian
authors: Department of Kidney and Pancreas Transplantation, Columbia University Medical Center, New York, New York, USA.
authors: David J
authors: DJ
authors: Cohen
authors: Department of Nephrology, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.
authors: Yahsou
authors: Y
authors: Delmas
authors: Beatson West Scotland Cancer Centre, Glasgow, UK.
authors: Kenneth
authors: K
authors: Douglas
authors: Division of Hematology/Oncology, Weill Cornell Medical College, New York, New York, USA.
authors: Richard R
authors: RR
authors: Furman
authors: Department of Surgery/Transplant Center, Houston Methodist Hospital, Houston, Texas, USA.
authors: Osama A
authors: OA
authors: Gaber
authors: Department of Renal Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors: Timothy
authors: T
authors: Goodship
authors: Department of Clinical Science, Intervention and Technology (CLINTEC), H9, Karolinska University Hospital, Stockholm, Sweden.
authors: Maria
authors: M
authors: Herthelius
authors: Department of Nephrology, CHU Hotel Dieu-Nantes, Nantes, France.
authors: Maryvonne
authors: M
authors: Hourmant
authors: Adult Kidney Transplant Unit, Université Paris Descartes & Hôpital Necker, Paris, France.
authors: Christophe M
authors: CM
authors: Legendre
authors: Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy.
authors: Giuseppe
authors: G
authors: Remuzzi
authors: Department of Nephrology, Newcastle University, Newcastle upon Tyne, UK.
authors: Neil
authors: N
authors: Sheerin
authors: Department of Nephrology, Istituto Giannina Gaslini, Genova, Italy.
authors: Antonella
authors: A
authors: Trivelli
authors: Department of Pediatric Nephrology, Assistance Publique-Hôpitaux de Paris, Hôpital Robert-Debré, Paris, France.
authors: Chantal
authors: C
authors: Loirat
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D065766:Atypical Hemolytic Uremic Syndrome / Q000097:blood / Q000188:drug therapy*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C481642:eculizumab
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