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

Authors: Schubert, Jörg¹; Hillmen, Peter²; Röth, Alexander³; Young, Neal S.⁴; Elebute, Modupe O.⁵; Szer, Jeffrey⁶; Gianfaldoni, Giacomo⁷; Socié, Gérard⁸; Browne, Paul⁹; Geller, Robert¹⁰; Rother, Russell P.¹⁰; Muus, Petra

Source: British Journal of Haematology, Volume 142, Number 2, July 2008 , pp. 263-272(10)

Publisher: Blackwell Publishing

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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.

Keywords: paroxysmal nocturnal haemoglobinuria; haemoglobin; haemolysis; transfusion

Document Type: Research article

DOI: 10.1111/j.1365-2141.2008.07183.x

Affiliations: 1: Internal Medicine I, Saarland University Medical School, Homburg Saar, Germany 2: Department of Haematology, St James's Institute of Oncology, Leeds, UK 3: Department of Haematology, University Hospital Essen, Germany 4: Cell Biology Section, Clinical Hematology Branch, NHLBI, NIH, Bethesda, MD, USA 5: Department of Cellular and Molecular Medicine, St. Georges Hospital, London, UK 6: Department of Clinical Haematology, Royal Melbourne Hospital, Melbourne, Australia 7: Department of Haematology, Azienda Ospedaliera Universitaria Careggi, Florence, Italy 8: Service d'Hematologie, Hospital Saint Louis and INSERM, Paris, France 9: Department of Haematology, St James Hospital, Dublin, Ireland 10: Alexion Pharmaceuticals Inc., Cheshire, CT, USA,

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