Long‐term safety and efficacy of sustained eculizumab treatment in patients with paroxysmal nocturnal haemoglobinuria

• Published in: British journal of haematology Vol. 162; no. 1; pp. 62 - 73
• Main Authors: Hillmen, Peter, Muus, Petra, Röth, Alexander, Elebute, Modupe O., Risitano, Antonio M., Schrezenmeier, Hubert, Szer, Jeffrey, Browne, Paul, Maciejewski, Jaroslaw P., Schubert, Jörg, Urbano‐Ispizua, Alvaro, Castro, Carlos, Socié, Gérard, Brodsky, Robert A.
• Format: Journal Article
• Language: English
• Published: Oxford Blackwell 01.07.2013; Blackwell Publishing Ltd
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Anemias. Hemoglobinopathies; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - therapeutic use; Biological and medical sciences; Blood Transfusion; Diseases of red blood cells; eculizumab; Female; Haematological Malignancy; haemolysis; Hematologic and hematopoietic diseases; Hemoglobins - metabolism; Hemoglobinuria, Paroxysmal - complications; Hemoglobinuria, Paroxysmal - diagnosis; Hemoglobinuria, Paroxysmal - drug therapy; Hemoglobinuria, Paroxysmal - mortality; Hemolysis; Humans; long‐term therapy; Male; Medical sciences; Middle Aged; paroxysmal nocturnal haemoglobinuria; phase III; Renal Insufficiency, Chronic - complications; Thrombosis - complications; Treatment Outcome; Tumors; Young Adult; Human; Hemolysis; Erythrocytic membrane disease; Hematology; Treatment efficiency; phase III; Hemopathy; Monoclonal antibody; Long term; Hemolytic anemia; Nocturnal paroxystic anemia; Cancerology; Treatment; haemolysis; Eculizumab; long-term therapy; paroxysmal nocturnal haemoglobinuria
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/bjh.12347

Summary 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.