A prospective, randomized, and crossover study of an activated prothrombin complex concentrate for secondary prophylaxis in patients with hemophilia A and inhibitors (Pro-FEIBA) : subject demographics and safety data

Introduction: Up to 30% of patients with severe hemophilia A develop inhibitors to factor VIII (FVIII). Inhibitors are persistent in 10% to 15% of these patients, placing them at high risk for severe hemorrhage and joint disease. Anecdotal evidence suggests FEIBA prophylaxis may decrease bleeding episodes in inhibitor patients. The primary objective of the Pro-FEIBA study was to assess whether FEIBA prophylaxis results in a significant reduction in relevant bleeds in hemophilia patients with persistent, high-responding inhibitors. Safety, pharmacoeconomics, and quality of life were secondary study objectives. Methods: A randomized, crossover design was used consisting of 6 months of prophylaxis at a dose of 85 U/kg ± 15% administered three times weekly on non-consecutive days, followed by a 3-month wash-out period and 6 months on on-demand therapy (target dose: 85 U/kg ± 15%), or vice versa. Inclusion criteria included (1) hemophilia A and a history of a high-titer inhibitor (> 5 Bethesda units), (2) ‡6 relevant bleeds in the past 6 months, (3) currently on on-demand therapy, (4) age > 2 years. Results: A total of 36 patients from 9 sites (Finland, France, Germany, Italy, Poland, Romania, Sweden, Turkey, and the United States) were enrolled. The mean patient age was 26.9 years (range: 2.8–67.9). Safety data are available and show 19 serious adverse events occurred, 1 of which was study-related (an allergic reaction). Conclusion: Preliminary data show FEIBA prophylaxis is safe and well tolerated in patients >2 years of age with hemophilia and high-responding inhibitors