Recombinant and Plasma-Based Factor VIII Products Confer Similar Risks of Inhibitor Development

To address whether the type of factor VIII (FVIII) product administered or switching among products is associated with the development of clinically relevant inhibitory antibodies in previously untreated children with severe hemophilia A, investigators at 29 European hemophilia treatment centers evaluated 574 consecutive patients born between 2000 and 2010. Data were collected on all infusions of plasma-based FVIII and first-, second- and third-generation recombinant FVIII products for up to 75 exposure days or until development of inhibitors.

Inhibitory antibodies developed in 177 of the 574 children (32.4%); 116 had a high-titer inhibitor, defined as a peak titer of at least 5 Bethesda units per milliliter. Plasma-derived FVIII products conferred a risk of inhibitor development that was similar to the risk with recombinant products (adjusted hazard ratio, 0.96; 95% confidence interval [CI], 0.62 to 1.49). As compared with third-generation full-length recombinant products (derived from the full-length complementary DNA sequence of human factor VIII), second-generation full-length products were associated with increased inhibitor risk (adjusted hazard ratio, 1.60; 95% CI, 1.08 to 2.37). The content of von Willebrand factor (vWF) in FVIII products and switching among products were not associated with the risk of inhibitor development.

The investigators concluded that recombinant and plasma-derived FVIII products confer similar risks of inhibitor development, and neither wWF content nor switching among products is associated with the risk of inhibitor development.