International Study Finds Similar Inhibitor Risk for FVIII Products

Horizons in Hemophilia, March 2013

Submitted by the National Hemophilia Foundation

Results of a recent international study published in The New England Journal of Medicine (NEJM) suggest that plasma-derived factor VIII (pdFVIII) products and recombinant factor VIII (rFVIII) products used to treat hemophilia A are associated with similar rates of inhibitor development. Overall, inhibitor antibodies to infused factor occur in approximately 25%-30% of children with severe hemophilia A. The study, funded through unrestricted research grants from Bayer HealthCare and Baxter BioScience, was designed to help test the theory that pdFVIII products are less susceptible to inhibitor formation than rFVIII therapies.

Data for the study, known as RODIN (Research Of Determinants of INhibitor Development Among Previously Treated Patients with Hemophilia), were drawn from a registry of pediatric hemophilia patients largely from Europe. The registry, the European Paediatric Network for Haemophilia Management Registry (PedNet) was established to allow for the investigation of the efficacy and side effects of FVIII therapies. The PedNet Registry encompasses 29 hemophilia treatment centers in 16 European countries, Israel and Canada. The lead author of the study was Samantha Gouw, MD, PhD, from the University Medical Center, Utrecht, Netherlands.

Gouw and her colleagues examined 574 previously untreated pediatric patients with severe hemophilia A born between 2000-2010. In all, 177 (30.8%) developed inhibitor antibodies after at least 75 exposure days to factor products; of those 116 (20.2%) showed a potent or “high-titer” inhibitor response. An inhibitor’s potency is measured by the Bethesda inhibitor assay, a blood test that determines the amount of antibodies directed against the clotting factor. Results of the assay are given in Bethesda units (BU). Patients with an inhibitor titer below 5 BU are said to have a weak, low-titer inhibitor; those with a titer of 5 or more BU have a potent, high-titer inhibitor.

Investigators reported that pdFVIII and rFVIII products were associated with comparable risks for inhibitor development. The data also showed that neither the use of products also containing von Willebrand factor nor switching from one FVIII product to another was linked to a heightened inhibitor risk. The study did, however, find that so-called “second generation rFVIII therapies,” in contrast to third generation rFVIII products, were linked to an increased risk for inhibitor development.   

The researchers noted that the findings necessitate follow-up studies. “There is no straightforward biologic explanation for a difference in immunogenicity among recombinant factor VIII products. Further studies are needed to verify these observations and to identify biologic explanations,” stated the authors. In several other published studies, second generation rFVIII products have not shown higher rates of inhibitor formation.    

The study, “Factor VIII Products and Inhibitor Development in Severe Hemophilia A,” was published in the January 17, 2013 issue of NEJM.

Source: HealthDay News and Medpage Today, January 17, 2013