title: Eculizumab, a terminal complement inhibitor, improves anaemia in patients with paroxysmal nocturnal haemoglobinuria.
abstract: In paroxysmal nocturnal haemoglobinuria (PNH), chronic destruction of PNH red blood cells (RBCs) by complement leads to anaemia and other serious morbidities. Eculizumab inhibits terminal complement-mediated PNH RBC destruction by targeting C5. In the phase III, double-blind, placebo-controlled, TRIUMPH study, eculizumab reduced haemolysis, stabilized haemoglobin levels, reduced transfusion requirements and improved fatigue in patients with PNH. Herein, we explored the effects of eculizumab on measures of anaemia in patients from the TRIUMPH study and the open-label SHEPHERD study, a more heterogeneous population. Eculizumab reduced haemolysis regardless of pretreatment transfusion requirements and regardless of whether or not patients became transfusion-dependent during treatment (P < 0.001). Reduction in haemolysis was associated with increased PNH RBC counts (P < 0.001) while reticulocyte counts remained elevated. Eculizumab-treated patients demonstrated significantly higher levels of haemoglobin as compared with placebo in TRIUMPH and relative to baseline levels in SHEPHERD (P < 0.001 for each study). Eculizumab lowered transfusion requirement across multiple pretreatment transfusion strata and eliminated transfusion support in a majority of both TRIUMPH and SHEPHERD patients (P < 0.001). Patients who required some transfusion support during treatment with eculizumab showed a reduction in haemolysis and transfusion requirements and an improvement in fatigue. Eculizumab reduces haemolysis and improves anaemia and fatigue, regardless of transfusion requirements.
authors.affiliation: Internal Medicine I, Saarland University Medical School, Homburg Saar, Germany. injsch@uks.eu
authors.forename: Jörg
authors.initials: J
authors.lastname: Schubert
authors.forename: Peter
authors.initials: P
authors.lastname: Hillmen
authors.forename: Alexander
authors.initials: A
authors.lastname: Röth
authors.forename: Neal S
authors.initials: NS
authors.lastname: Young
authors.forename: Modupe O
authors.initials: MO
authors.lastname: Elebute
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Szer
authors.forename: Giacomo
authors.initials: G
authors.lastname: Gianfaldoni
authors.forename: Gérard
authors.initials: G
authors.lastname: Socié
authors.forename: Paul
authors.initials: P
authors.lastname: Browne
authors.forename: Robert
authors.initials: R
authors.lastname: Geller
authors.forename: Russell P
authors.initials: RP
authors.lastname: Rother
authors.forename: Petra
authors.initials: P
authors.lastname: Muus
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001803:Blood Transfusion; D004311:Double-Blind Method; D004906:Erythrocyte Count; D004912:Erythrocytes; D005221:Fatigue; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood / Q000188:drug therapy*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D006454:Hemoglobins; C481642:eculizumab