Long‐term safety and efficacy of sustained eculizumab treatment in patients with paroxysmal nocturnal haemoglobinuria |
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| Authors: | Peter Hillmen Petra Muus Alexander Röth Modupe O. Elebute Antonio M. Risitano Hubert Schrezenmeier Jeffrey Szer Paul Browne Jaroslaw P. Maciejewski Jörg Schubert Alvaro Urbano‐Ispizua Carlos de Castro Gérard Socié Robert A. Brodsky |
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| Affiliation: | 1. St James's University Hospital, , Leeds, UK;2. Radboud University Nijmegen Medical Centre, , Nijmegen, The Netherlands;3. University of Duisburg‐Essen, , Essen, Germany;4. Department of Haematological Medicine, King's College Hospital, , London, UK;5. Federico II University, , Naples, Italy;6. Institute of Clinical Transfusion Medicine and Immunogenetics, German Red Cross Blood Transfusion Service and Institute of Transfusion Medicine, University of Ulm, , Ulm, Germany;7. Royal Melbourne Hospital, , Melbourne, Australia;8. St. James's Hospital, Trinity College Dublin, , Dublin, Ireland;9. Taussig Cancer Center, Cleveland Clinic, , Cleveland, OH, USA;10. Saarland University Medical School, , Homburg‐Saarland, Germany;11. Grupo de Trabajo de HPN de la Sociedad Espa?ola de Hematología y Hemoterapia, , Barcelona, Spain;12. Duke University Medical Center, , Durham, NC, USA;13. H?pital Saint‐Louis and Institut National de la Santé et de la Recherche Médicale (INSERM), , Paris, France;14. Johns Hopkins University School of Medicine, , Baltimore, MD, USA |
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| Abstract: | Paroxysmal nocturnal haemoglobinuria (PNH) is characterized by chronic, uncontrolled complement activation resulting in elevated intravascular haemolysis and morbidities, including fatigue, dyspnoea, abdominal pain, pulmonary hypertension, thrombotic events (TEs) and chronic kidney disease (CKD). The long‐term safety and efficacy of eculizumab, a humanized monoclonal antibody that inhibits terminal complement activation, was investigated in 195 patients over 66 months. Four patient deaths were reported, all unrelated to treatment, resulting in a 3‐year survival estimate of 97·6%. All patients showed a reduction in lactate dehydrogenase levels, which was sustained over the course of treatment (median reduction of 86·9% at 36 months), reflecting inhibition of chronic haemolysis. TEs decreased by 81·8%, with 96·4% of patients remaining free of TEs. Patients also showed a time‐dependent improvement in renal function: 93·1% of patients exhibited improvement or stabilization in CKD score at 36 months. Transfusion independence increased by 90·0% from baseline, with the number of red blood cell units transfused decreasing by 54·7%. Eculizumab was well tolerated, with no evidence of cumulative toxicity and a decreasing occurrence of adverse events over time. Eculizumab has a substantial impact on the symptoms and complications of PNH and results a significant improvement in patient survival. |
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| Keywords: | eculizumab paroxysmal nocturnal haemoglobinuria phase III long‐term therapy haemolysis |
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