title: Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria.
abstract: 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 3 eculizumab PNH clinical studies, which recruited patients between 2002 and 2005 (n = 195); patients from these studies continued treatment in the current multinational open-label extension study. Thromboembolism rate with eculizumab treatment was compared with the pretreatment rate in the same patients. The TE event rate with eculizumab treatment was 1.07 events/100 patient-years compared with 7.37 events/100 patient-years (P < .001) prior to eculizumab treatment (relative reduction, 85%; absolute reduction, 6.3 TE events/100 patient-years). With equalization of the duration of exposure before and during treatment for each patient, TE events were reduced from 39 events before 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 no. NCT00122317).
authors: Leeds General Infirmary, Leeds, United Kingdom. peter.hillmen@nhs.net
authors: Peter
authors: P
authors: Hillmen
authors: Petra
authors: P
authors: Muus
authors: Ulrich
authors: U
authors: Dührsen
authors: Antonio M
authors: AM
authors: Risitano
authors: Jörg
authors: J
authors: Schubert
authors: Lucio
authors: L
authors: Luzzatto
authors: Hubert
authors: H
authors: Schrezenmeier
authors: Jeffrey
authors: J
authors: Szer
authors: Robert A
authors: RA
authors: Brodsky
authors: Anita
authors: A
authors: Hill
authors: Gerard
authors: G
authors: Socié
authors: Monica
authors: M
authors: Bessler
authors: Scott A
authors: SA
authors: Rollins
authors: Leonard
authors: L
authors: Bell
authors: Russell P
authors: RP
authors: Rother
authors: Neal S
authors: NS
authors: Young
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D051056:Complement Inactivating Agents / Q000008:administration & dosage*; D003165:Complement System Proteins; D005260:Female; D005500:Follow-Up Studies; D006457:Hemoglobinuria, Paroxysmal / Q000150:complications / Q000188:drug therapy*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012307:Risk Factors; D013923:Thromboembolism / Q000209:etiology / Q000517:prevention & control*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D051056:Complement Inactivating Agents; D003165:Complement System Proteins; C481642:eculizumab