Eculizumab, a terminal complement inhibitor, improves anaemia in patients with paroxysmal nocturnal haemoglobinuria

Abstract

Summary 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.

How I treat paroxysmal nocturnal hemoglobinuria

“…In classic PNH patients who are transfusion-dependent, a marked decrease in red cell transfusions is observed in virtually all patients, with more than 50% achieving transfusion independence. 39,40,44 Breakthrough intravascular hemolysis and a return of PNH symptoms occur in less than 2% of PNH patients treated with eculizumab. This typically occurs a day or two before the next scheduled dose and is accompanied a spike in the LDH level.…”

Chronic treatment of paroxysmal nocturnal hemoglobinuria patients with eculizumab: safety, efficacy, and unexpected laboratory phenomena

“…The SHEPHERD study, an open-label phase-III safety and efficacy trial that enrolled a more heterogeneous population of patients with PNH (including those with significant thrombocytopenia and minimal transfusion requirements) showed similar benefits of eculizumab [13,14].…”

Paroxysmal Nocturnal Haemoglobinuria Presenting with Acute Kidney Injury: A Case Report

“…Özellikle bitkinlik, trombozlar, transfüzyon bağımlılığı olan, sık ağrı atakları geçiren, renal yetmezlik ve diğer end organ komplikasyonları gelişmiş hastalarda uygun bir tedavi seçe-neğidir. İntravasküler hemolizi ve kan transfüzyonu gereksinimini belirgin olarak azaltır (7) . Olgumuza da eculizumab başlandı.…”