Indirect comparisons of efficacy and weekly factor consumption during continuous prophylaxis with recombinant factor VIII Fc fusion protein and conventional recombinant factor VIII products

Introduction Recombinant factor VIII ( rFVIII ) products with extended half‐lives have the potential to improve adherence and outcomes in haemophilia beyond the results obtained with conventional rFVIII products. Aim In the absence of head‐to‐head comparisons, annualized bleed rates ( ABR s) and weekly factor consumption with rFVIII Fc fusion protein ( rFVIIIF c) and conventional rFVIII products were indirectly compared using studies of continuous prophylaxis. Methods A systematic literature review was conducted to identify studies of rFVIII products for comparison with rFVIIIF c in the continuous prophylactic treatment of previously treated adolescents and adults with moderate and severe haemophilia A. Mean ABR s were compared between rFVIIIF c and individual rFVIII studies and between rFVIIIF c and a pooled measure for rFVIII estimated by meta‐analysis. Comparisons of factor consumption were based on mean or median weekly factor consumption. Results Results from seven studies of conventional rFVIII products (injections 2–4 times week −1 ) were compared with rFVIIIF c (injections 1.4–2.4 times week −1 ). The pooled mean ABR for rFVIII products was significantly higher compared with rFVIIIF c (difference = 2.0; P = 0.007). Compared with most rFVIII studies, the reported weekly factor consumption was lower with rFVIIIF c [mean differences = 15.5–21.8 IU kg −1 week −1 (17–26%); median differences = 12.7–29.8 IU kg −1 week −1 (16–37%)]. In one comparison, mean weekly factor consumption with rFVIII was significantly lower but mean ABR was significantly higher than rFVIIIF c. Conclusion Prophylaxis with rFVIIIF c may be associated with improved bleeding rates and lower weekly factor consumption than more frequently injected rFVIII products. Relative to rFVIII products with similar bleeding rates, results indicate that rFVIIIF c is associated with reduced weekly factor consumption while requiring fewer prescribed injections.