Prophylaxis with Anti-Inhibitor Coagulant Complex Reduces Bleeding Episodes

Prophylactic treatment with an anti-inhibitor coagulant complex (FEIBA NF [Factor Eight Inhibitor Bypassing Activity], Baxter Healthcare) reduced the median annualized bleeding rate (ABR) more than three-fold as compared with on-demand treatment with the product to control acute hemorrhages, according to a Phase III study of 36 subjects with hemophilia A or B and inhibitory alloantibodies to factor VIII or factor IX.

Over a one-year period, 17 subjects with high-titer or low-titer inhibitors refractory to factor VIII or factor IX replacement therapy were treated prophylactically with 85 ± 15 U/kg bolus intravenous doses of FEIBA NF every other day, while 19 subjects received FEIBA NF on demand at the discretion of the individual investigator. The median ABR during prophylaxis was 7.9 events, compared with 28.7 events during on-demand treatment — a statistically significant 72.5 percent reduction in relation to the on-demand treatment arm (P = 0.0003).

Three subjects (17.6 percent) on prophylaxis experienced no bleeding episodes, whereas none receiving on-demand treatment were free of bleeding episodes. The prophylaxis group reported greater reductions in pain scores and fewer days absent from work or school because of bleeding episodes. A post hoc analysis comparing bleeding events during the 12 months prior to study initiation against the 12-month study period found 12 of 16 prophylaxis group subjects experienced a reduction in bleeding episodes, compared with just two of 19 on-demand group subjects. Total usage of FEIBA NF was three times higher in the prophylaxis group than in the on-demand group (P = 0.0067). The safety of prophylaxis was found to be comparable to that of on-demand treatment; no thromboembolic events were identified in either treatment arm.

[Editorial note: In December 2013, the U.S. Food and Drug Administration expanded the approved indications for FEIBA NF to include routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with hemophilia A or B who have developed inhibitors.]