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Blood, 15 February 2008, Vol. 111, No. 4, pp. 1840-1847.
Prepublished online as a Blood First Edition Paper on November 30, 2007; DOI 10.1182/blood-2007-06-094136.
 Previous Article | Next Article 
Submitted June 6, 2007
Accepted November 18, 2007
Multicenter phase III study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria
Robert A. Brodsky*, Neal S. Young, Elisabetta Antonioli, Antonio M Risitano, Hubert Schrezenmeier, Jorg Schubert, Anna Gaya Valls, Luke Coyle, Carlos de Castro, Chieh-Lin Fu, Jaroslaw P. Maciejewski, Monica Bessler, Henk-Andre Kroon, Russell P. Rother, and Peter Hillmen
Department of Medicine, Division of Hematology, The Johns Hopkins Medical Institutions, Baltimore, MD, United States
National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, United States
Department of Hematology, University of Florence, Florence, Italy
Department of Hematology, Federico II University of Naples, Naples, Italy
Institute of Transfusion Medicine, University Hospital, Ulm, Germany
Deparment of Internal Medicine, Saarland University Medical School, Homburg-Saarland, Germany
Department of Hematology, Hospital Clinic of Barcelona, Barcelona, Spain
Department of Hematology, Royal North Shore Hospital, St. Leonards, New South Wales, Australia
Department of Medical Oncology, Duke University Medical Center, Durham, NC, United States
Department of Hematology/Oncology, Cleveland Clinic Florida, Weston, FL, United States
Experimental Hematology, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH, United States
Department of Hematology, Washington University in St. Louis, St. Louis, MO, United States
Department of Research, Alexion Pharmaceuticals, Inc, Cheshire, CT, United States
Department of Haematology, Leeds General Infirmary, Leeds, United Kingdom
* Corresponding author; email: brodsro{at}jhmi.edu.
The terminal complement inhibitor eculizumab was recently shown to be effective and well-tolerated in patients with paroxysmal nocturnal hemoglobinuria (PNH). Here, we extended these observations with results from an open-label, non-placebo controlled, 52-week, phase III clinical safety and efficacy study evaluating eculizumab in a broader PNH patient population. Eculizumab was administered by intravenous infusion at 600 mg every 7 ± 2 days for 4 weeks; 900 mg 7 ± 2 days later; followed by 900 mg every 14 ± 2 days for 52 weeks. Ninety-seven patients at 33 international sites were enrolled. Patients treated with eculizumab responded with an 87% reduction in hemolysis, as measured by lactate dehydrogenase levels (P < 0.001). Baseline fatigue scores in the FACIT-Fatigue instrument improved by 12.2 ± 1.1 points (P < 0.001). Eculizumab treatment led to an improvement in anemia. The increase in hemoglobin occurred despite a reduction in transfusion requirements from a median of 8.0 units packed red cells per patient pre-treatment to 0.0 units per patient during the study (P < 0.001). Overall, transfusions were reduced 52% from a mean of 12.3 to 5.9 units per patient. Forty-nine (51%) patients achieved transfusion independence for the entire 52 week period. Improvements in hemolysis, fatigue, and transfusion requirements with eculizumab were independent of baseline levels of hemolysis and degree of thrombocytopenia. Quality of life measures were also broadly improved with eculizumab treatment. This study demonstrates that the beneficial effects of eculizumab treatment in patients with PNH are applicable to a broader population of PNH patients than previously studied. This trial is registered at http://clinicaltrials.gov as NCT00130000.
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