There was no difference between serum-derived and recombinant factor VIII products, but there was a difference between third- and second-generation recombinant products with respect to the formation of antibodies, or inhibitors, that can make the products ineffective, according to a study of previously untreated children with severe hemophilia A.

The content of von Willebrand factor in the various products and switching between products did not increase risk for inhibitor development, according to the study, which was published in The New England Journal of Medicine (2013:368:231-239).

The results of the observational study were unexpected, according to Asad Patanwala, PharmD, an assistant professor in the Department of Pharmacy Practice and Science at the University of Arizona, in Tucson. “The findings were important ones,” said Dr. Patanwala. “It was surprising that there were differences in the outcome between second- and third-generation recombinant products. The authors were unable to explain this using any biological rationales.”

A multinational team evaluated 574 consecutive patients with severe hemophilia A who were born between 2000 and 2010, and collected data on all clotting-factor administration for up to 75 exposure days. The primary outcome was inhibitor development, which was defined as at least two positive inhibitor tests with decreased in vivo recovery of factor VIII levels.

Inhibitory antibodies developed in 177 of the 574 children (32.4%); 116 patients had a high-titer inhibitory antibody, defined as a peak titer of at least 5 Bethesda units/mL (22.4%). Plasma-derived products conferred a risk for inhibitor development that was similar to the risk with recombinant products (adjusted hazard ratio as compared with recombinant products, 0.96; 95% confidence interval [CI], 0.62-1.49). 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 an increased risk for inhibitor development (adjusted hazard ratio, 1.60; 95% CI, 1.08-2.37).

Dr. Patanwala said that this well-designed study might change the way hemophilia A is treated in the not-too-distant future. “When patients with hemophilia present with bleeding to an acute care setting, they are usually given the product they always use. In some cases it may not be available at that hospital. Perhaps hematologists would be more willing to use an alternative product,” said Dr. Patanwala. “Also, perhaps the choice of product used can be based on other criteria rather than inhibitor formation when patients are initiated on therapy.”

Author H. Marijke van den Berg, MD, declined to comment on the study on behalf of the study group. The study was funded by Bayer Healthcare and Baxter BioScience.


Dr. Patanwala reported no relevant financial conflicts of interest.