title: The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria.
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.
authors.affiliation: Leeds General Infirmary, Leeds, United Kingdom. peter.hillmen@nhs.net
authors.forename: Peter
authors.initials: P
authors.lastname: Hillmen
authors.forename: Neal S
authors.initials: NS
authors.lastname: Young
authors.forename: Jörg
authors.initials: J
authors.lastname: Schubert
authors.forename: Robert A
authors.initials: RA
authors.lastname: Brodsky
authors.forename: Gerard
authors.initials: G
authors.lastname: Socié
authors.forename: Petra
authors.initials: P
authors.lastname: Muus
authors.forename: Alexander
authors.initials: A
authors.lastname: Röth
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Szer
authors.forename: Modupe O
authors.initials: MO
authors.lastname: Elebute
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Nakamura
authors.forename: Paul
authors.initials: P
authors.lastname: Browne
authors.forename: Antonio M
authors.initials: AM
authors.lastname: Risitano
authors.forename: Anita
authors.initials: A
authors.lastname: Hill
authors.forename: Hubert
authors.initials: H
authors.lastname: Schrezenmeier
authors.forename: Chieh-Lin
authors.initials: CL
authors.lastname: Fu
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Maciejewski
authors.forename: Scott A
authors.initials: SA
authors.lastname: Rollins
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Mojcik
authors.forename: Russell P
authors.initials: RP
authors.lastname: Rother
authors.forename: Lucio
authors.initials: L
authors.lastname: Luzzatto
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D003182:Complement C5 / Q000276:immunology*; D004311:Double-Blind Method; D017707:Erythrocyte Transfusion; D005221:Fatigue; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood / Q000188:drug therapy* / Q000628:therapy; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011788:Quality of Life
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003182:Complement C5; D006454:Hemoglobins; C481642:eculizumab