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Blood, 1 December 2007, Vol. 110, No. 12, pp. 4123-4128.
Prepublished online as a Blood First Edition Paper on August 16, 2007; DOI 10.1182/blood-2007-06-095646.
 Previous Article | Next Article 
Submitted June 13, 2007
Accepted August 9, 2007
Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria
Peter Hillmen*, Petra Muus, Ulrich Duhrsen, Antonio M Risitano, Jorg Schubert, Lucio Luzzatto, Hubert Schrezenmeier, Jeffrey Szer, Robert A Brodsky, Anita Hill, Gerard Socie, Monica Bessler, Scott A Rollins, Leonard Bell, Russell P Rother, and Neal S Young
Department of Haematology, Leeds General Infirmary, Leeds, United Kingdom
Department of Hematology, Radboud University Medical Center, Nijmegen, Netherlands
Centrum fur Innere Medizin, University of Essen, Essen, Germany
Dipartimento di Biochimica e Biotecnologie Mediche, Federico II University, Naples, Italy
Internal Medicine I, Saarland University Medical School, Homburg/Saarland, Germany
Department of Hematology, Istituto Toscano Tumori, Florence, Italy
Clinical Transfusion Medicine and Immunogenetics, Institute of Transfusion Medicine, University Hospital, Ulm, Germany
Clinical Haematology & BMT Service, Royal Melbourne Hospital, Melbourne, Australia
Department of Medicine and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
Department of Hematology / Stem Cell Transplantation, Hospital Saint-Louis and INSERM, Paris, France
Department of Internal Medicine/Division of Hematology, Washington University School of Medicine, St. Louis, MO, United States
Alexion Pharmaceuticals, Inc., Cheshire, CT, United States
Hematology Branch, National Heart, Lung, and Blood Institute, Bethesda, MD, United States
* Corresponding author; email: peter.hillmen{at}nhs.net.
Hemolysis and hemoglobinemia contribute to serious clinical sequelae in hemolytic disorders. In paroxysmal nocturnal hemoglobinuria (PNH) patients, hemolysis can contribute to thromboembolism (TE), the most feared complication in PNH, and the leading cause of disease-related deaths. We evaluated whether long-term treatment with the complement inhibitor eculizumab reduces the rate of TE in patients with PNH. Clinical trial participants included all patients in the three eculizumab PNH clinical studies which enrolled between 2002 and 2005 (n=195), and their continued treatment in a common multinational open-label extension study. Thromboembolism rate with eculizumab treatment was compared to the pre-treatment rate in the same patients. The TE event rate with eculizumab treatment was 1.07 events/100 patient-years compared to 7.37 events/100 patient-years (P<.001) prior to eculizumab treatment (relative reduction of 85%, absolute reduction 6.3 TE events/100 patient-years). With equalization of the duration of exposure before and during treatment for each patient, TEs were reduced from 39 events pre-eculizumab to 3 events during eculizumab (P<.001). The TE event rate in antithrombotic-treated patients (n=103) was reduced from 10.61 to 0.62 events/100 patient-years with eculizumab treatment (P<.001). These results show that eculizumab treatment reduces the risk of clinical thromboembolism in patients with PNH. This study is registered at http://clinicaltrials.gov (Study ID:#NCT00122317).
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