Matching-adjusted indirect comparisons of efficacy of BAY 81-8973 vs two recombinant factor VIII for the prophylactic treatment of severe hemophilia A.

Background: No head-to-head trials comparing recombinant factor VIII (rFVIII) products currently exist. This was a matching-adjusted indirect comparison (MAIC) study of efficacy of BAY 81-8973 with antihemophilic factor (recombinant) plasma/albumin-free method (rAHFPFM) and turoctocog alfa for the prophylaxis of severe hemophilia A. Methods: A systematic literature review was conducted to identify trials of rAHF-PFM and turoctocog alfa. Comparisons were conducted using BAY 81-8973 individual patient data (IPD) from LEOPOLD trials and published data from rAHF-PFM and turoctocog alfa trials. Differences in outcome reporting were reconciled using transformation of BAY 81-8973 IPD. Patients in pooled LEOPOLD trials were weighted to match baseline characteristics for rAHFPFM or turoctocog alfa trials using MAICs. After matching, annualized bleed rates (ABRs) were compared using weighted t-tests. Results: Two rAHF-PFM trials and one turoctocog alfa trial were identified. In these trials, rFVIIIs were dosed thrice weekly or every other day; in LEOPOLD trials, BAY 81-8973 was dosed twice- or thrice weekly. Three MAICs were conducted because the two rAHF-PFM trials calculated ABRs differently, matching for age, race, and weight (turoctocog alfa only). BAY 81-8973 had similar ABR of all bleeds vs rAHF-PFM (two trials: 4.8 vs 6.3, 1.9 vs 1.8 [square root transform]) and lower ABR of spontaneous bleeds and trauma bleeds (2.6 vs 4.1, 2.1 vs 4.7; both P<0.05). BAY 81-8973 showed lower ABR of all bleeds and spontaneous bleeds vs turoctocog alfa (4.3 vs 6.5, 2.8 vs 4.3; both P<0.05) and similar ABR of trauma bleeds (1.5 vs 1.6). In subgroup analysis, twice-weekly BAY 81-8973 had similar ABRs of all bleeds, spontaneous bleeds, and trauma bleeds compared to rAHF-PFM and turoctocog alfa. Conclusion: This indirect comparison found that prophylaxis with BAY 81-8973, even including the lower frequency of two times a week and lower factor VIII consumption, has efficacy comparable to rAHF-PFM and turoctocog alfa, which were dosed thrice weekly or every other day. The use of IPD enabled adjustments for differences in calculation of ABRs and population characteristics between trials. [ABSTRACT FROM AUTHOR]