Randomized comparison of prophylaxis and on-demand regimens with FEIBA NF in the treatment of haemophilia A and B with inhibitors

Haemophilia. 2014 Jan;20(1):65-72. doi: 10.1111/hae.12246. Epub 2013 Aug 1.

Abstract

Factor replacement therapy for the treatment of moderate to severe haemophilia A and B can be complicated by the production of inhibitory alloantibodies to factor VIII (FVIII) or factor IX. Treatment with the nanofiltered anti-inhibitor coagulant complex, Factor Eight Inhibitor Bypassing Activity (FEIBA NF), is a key therapeutic option for controlling acute haemorrhages in patients with high-titre inhibitors or low-titre inhibitors refractory to replacement therapy. Given the high risk for morbidity and mortality in haemophilia patients with inhibitors to FVIII or FIX, we conducted this Phase 3 prospective study to evaluate whether prophylaxis with FEIBA NF is a safe and effective treatment option. Over a 1-year period, 17 subjects were treated prophylactically (85 ± 15 U kg(-1) every other day) while 19 subjects were treated on demand. The median (IQR) annualized bleeding rate (ABR) during prophylaxis was 7.9 (8.1), compared to 28.7 (32.3) during on-demand treatment, which amounts to a 72.5% reduction and a statistically significant difference in ABRs between arms (P = 0.0003). Three (17.6%) subjects (ITT) on prophylaxis experienced no bleeding episodes, whereas none treated on demand were bleeding episode-free. Total utilization of FEIBA NF for the treatment of bleeding episodes was significantly higher during on-demand therapy than prophylaxis (P = 0.0067). There were no differences in the rates of related adverse events between arms. This study demonstrates that FEIBA prophylaxis significantly reduces all types of bleeding compared with on-demand treatment, and the safety of prophylaxis is comparable to that of on-demand treatment.

Keywords: FEIBA; Prophylaxis; haemophilia A/B; inhibitors; on-demand.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Blood Coagulation Factor Inhibitors
  • Blood Coagulation Factors / administration & dosage
  • Blood Coagulation Factors / adverse effects
  • Blood Coagulation Factors / therapeutic use*
  • Child
  • Factor IX / administration & dosage
  • Factor IX / adverse effects
  • Factor IX / therapeutic use*
  • Factor VIII / administration & dosage
  • Factor VIII / adverse effects
  • Factor VIII / therapeutic use*
  • Hemophilia A / blood
  • Hemophilia A / complications
  • Hemophilia A / drug therapy*
  • Hemophilia B / blood
  • Hemophilia B / complications
  • Hemophilia B / drug therapy*
  • Hemorrhage / etiology
  • Hemorrhage / therapy
  • Humans
  • Male
  • Middle Aged
  • Premedication*
  • Quality of Life
  • Treatment Outcome
  • Young Adult

Substances

  • Blood Coagulation Factor Inhibitors
  • Blood Coagulation Factors
  • Factor VIII
  • Factor IX
  • anti-inhibitor coagulant complex