Eculizumab, a terminal complement inhibitor, improves anaemia in patients with paroxysmal nocturnal haemoglobinuria.
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.
Schubert
Jörg
J
Internal Medicine I, Saarland University Medical School, Homburg Saar, Germany. injsch@uks.eu
Hillmen
Peter
P
Röth
Alexander
A
Young
Neal S
NS
Elebute
Modupe O
MO
Szer
Jeffrey
J
Gianfaldoni
Giacomo
G
Socié
Gérard
G
Browne
Paul
P
Geller
Robert
R
Rother
Russell P
RP
Muus
Petra
P
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
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D006454:Hemoglobins; C481642:eculizumab