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Previous Volume 355:1233-1243 September 21, 2006 Number 12 Next

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ABSTRACT

Background We tested the safety and efficacy of eculizumab, a humanized monoclonal antibody against terminal complement protein C5 that inhibits terminal complement activation, in patients with paroxysmal nocturnal hemoglobinuria (PNH).

Methods We conducted a double-blind, randomized, placebo-controlled, multicenter, phase 3 trial. Patients received either placebo or eculizumab intravenously; eculizumab was given at a dose of 600 mg weekly for 4 weeks, followed 1 week later by a 900-mg dose and then 900 mg every other week through week 26. The two primary end points were the stabilization of hemoglobin levels and the number of units of packed red cells transfused. Biochemical indicators of intravascular hemolysis and the patients' quality of life were also assessed.

Results Eighty-seven patients underwent randomization. Stabilization of hemoglobin levels in the absence of transfusions was achieved in 49% (21 of 43) of the patients assigned to eculizumab and none (0 of 44) of those assigned to placebo (P<0.001). During the study, a median of 0 units of packed red cells was administered in the eculizumab group, as compared with 10 units in the placebo group (P<0.001). Eculizumab reduced intravascular hemolysis, as shown by the 85.8% lower median area under the curve for lactate dehydrogenase plotted against time (in days) in the eculizumab group, as compared with the placebo group (58,587 vs. 411,822 U per liter; P<0.001). Clinically significant improvements were also found in the quality of life, as measured by scores on the Functional Assessment of Chronic Illness Therapy-Fatigue instrument (P<0.001) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. Of the 87 patients, 4 in the eculizumab group and 9 in the placebo group had serious adverse events, none of which were considered to be treatment-related; all these patients recovered without sequelae.

Conclusions Eculizumab is an effective therapy for PNH. (ClinicalTrials.gov number, NCT00122330 [ClinicalTrials.gov] .)

Source Information

From Leeds General Infirmary, Leeds, United Kingdom (P.H., A.H.); National Heart, Lung, and Blood Institute, Bethesda, MD (N.S.Y.); Saarland University Medical School, Homburg-Saarland, Germany (J. Schubert); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (R.A.B.); Hôpital Saint-Louis and INSERM, Paris (G.S.); Radboud University Medical Center, Nijmegen, the Netherlands (P.M.); University Hospital of Essen, Essen, Germany (A.R.); Royal Melbourne Hospital, Parkville, Melbourne, Australia (J. Szer); St. George Hospital, London (M.O.E.); City of Hope National Medical Center and Beckman Research Institute, Duarte, CA (R.N.); St. James' Hospital, Trinity College Dublin, Dublin (P.B.); Federico II University, Naples (A.M.R.); the Institute of Transfusion Medicine, University Hospital, Ulm, Germany (H.S.); Cleveland Clinic Florida, Weston, FL (C.-L.F.); Taussig Cancer Center, Cleveland Clinic Foundation, Cleveland (J.M.); Alexion Pharmaceuticals, Cheshire, CT (S.A.R., C.F.M., R.P.R.); and Istituto Toscano Tumori, Florence, Italy (L.L.).

Address reprint requests to Dr. Hillmen at the Department of Haematology, Leeds General Infirmary, Great George St., Leeds LS1 3EX, United Kingdom, or at peter.hillmen{at}nhs.net.

Full Text of this Article

Related Letters:

Eculizumab in Paroxysmal Nocturnal Hemoglobinuria
Kathula S. K., Singh J., Malani A. K., Pabla M., Takita M., Matsumura T., Kami M., Pride Y. B., Hillmen P.
Extract | Full Text | PDF  
N Engl J Med 2006; 355:2786-2788, Dec 28, 2006. Correspondence

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