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Clinical benefit of eculizumab in patients with no transfusion history in the International Paroxysmal Nocturnal Haemoglobinuria Registry
Author(s) -
Almeida Antonio M.,
Bedrosian Camille,
Cole Alexander,
Muus Petra,
Schrezenmeier Hubert,
Szer Jeff,
Rosse Wendell F.
Publication year - 2017
Publication title -
internal medicine journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.596
H-Index - 70
eISSN - 1445-5994
pISSN - 1444-0903
DOI - 10.1111/imj.13523
Subject(s) - eculizumab , medicine , haemolysis , population , paroxysmal nocturnal hemoglobinuria , gastroenterology , antibody , immunology , environmental health , complement system
Background Eculizumab reduces intravascular haemolysis and improves disease symptoms in patients with paroxysmal nocturnal haemoglobinuria ( PNH ). Aims To characterise, in a real‐world setting, the effect of eculizumab in patients with haemolytic PNH (lactase dehydrogenase ( LDH ) ≥ 1.5 upper limit of normal) and no history of red blood cell transfusion, including those with high disease activity ( HDA ). Methods Three populations from the International PNH Registry were studied: (i) non‐transfused, untreated; (ii) non‐transfused, eculizumab‐treated and (iii) transfused, eculizumab‐treated (≥1 transfusions in 6 months prior to eculizumab initiation). Using multivariate linear regression, the primary outcome was mean absolute change from baseline to 6 months in LDH (U/L) in non‐transfused patients who were treated with eculizumab versus those who remained untreated. Secondary outcomes were mean changes in functional assessment of chronic illness therapy ( FACIT )‐Fatigue and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire ( EORTC‐QLQ )‐ C30 Fatigue scores from baseline to last available assessment. Results The study population included (i) 144 non‐transfused, untreated patients; (ii) 45 non‐transfused, eculizumab‐treated patients and (iii) 105 transfused, eculizumab‐treated patients. Of these, 136/144, 43/45 and 99/105 had HDA respectively. Compared with untreated patients, non‐transfused, treated patients had greater absolute reduction in LDH (−1318.8 vs −39.4; P < 0.001) and greater percentage reduction in LDH (−69.9 vs −1.6%; P < 0.001). Clinically meaningful improvements in FACIT ‐Fatigue (73.7 vs 24.6%, respectively) and in EORTC‐QLQ‐C30 (84.2 vs 33.3%, respectively) were observed. Non‐transfused, treated patients with HDA had significantly reduced LDH levels ( P < 0.001) and clinically meaningful improvements in FACIT ‐Fatigue ( P = 0.003) and EORTC‐QLQ‐C30 ( P = 0.020) versus untreated patients. Conclusion Significant LDH reduction and clinically meaningful improvement in fatigue were observed in patients with PNH and HDA treated with eculizumab versus untreated patients, irrespective of transfusion history.