Clinical benefit of eculizumab in patients with no transfusion history in the International Paroxysmal Nocturnal Haemoglobinuria Registry

Intern Med J. 2017 Sep;47(9):1026-1034. doi: 10.1111/imj.13523.

Abstract

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.

Keywords: eculizumab; high disease activity; outcome; paroxysmal nocturnal haemoglobinuria; transfusion.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Blood Transfusion*
  • Female
  • Hemoglobinuria, Paroxysmal / diagnosis
  • Hemoglobinuria, Paroxysmal / drug therapy*
  • Hemoglobinuria, Paroxysmal / epidemiology*
  • Humans
  • Internationality*
  • Male
  • Middle Aged
  • Prospective Studies
  • Registries*
  • Treatment Outcome
  • Young Adult

Substances

  • Antibodies, Monoclonal, Humanized
  • eculizumab