title: Randomized comparison of prophylaxis and on-demand regimens with FEIBA NF in the treatment of haemophilia A and B with inhibitors.
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.
authors.affiliation: UNIFESP, São Paulo, Brazil.
authors.forename: S V
authors.initials: SV
authors.lastname: Antunes
authors.forename: S
authors.initials: S
authors.lastname: Tangada
authors.forename: O
authors.initials: O
authors.lastname: Stasyshyn
authors.forename: V
authors.initials: V
authors.lastname: Mamonov
authors.forename: J
authors.initials: J
authors.lastname: Phillips
authors.forename: N
authors.initials: N
authors.lastname: Guzman-Becerra
authors.forename: A
authors.initials: A
authors.lastname: Grigorian
authors.forename: B
authors.initials: B
authors.lastname: Ewenstein
authors.forename: W-Y
authors.initials: WY
authors.lastname: Wong
mesh_terms: D000293:Adolescent; D000328:Adult; D019774:Blood Coagulation Factor Inhibitors; D001779:Blood Coagulation Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D005164:Factor IX / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005169:Factor VIII / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006467:Hemophilia A / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D002836:Hemophilia B / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D006470:Hemorrhage / Q000209:etiology / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D011292:Premedication; D011788:Quality of Life; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D019774:Blood Coagulation Factor Inhibitors; D001779:Blood Coagulation Factors; D005169:Factor VIII; D005164:Factor IX; C065655:anti-inhibitor coagulant complex
keywords: FEIBA; Prophylaxis; haemophilia A/B; inhibitors; on-demand
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