A combined analysis of the results from 3 studies revealed that factor VIII inhibitor development was significantly lower with the use of third‐generation recombinant factor VIII (rFVIII) products compared with the use of second‐generation rFVIII products in previously untreated patients with severe hemophilia A.
The study, with results published in Haemophilia, used data from the Research of Determinants of Inhibitor Development (PedNet study group), the FranceCoag Network, and the United Kingdom Haemophilia Centre Doctors’ Organisation (UKHCDO) studies, which tested the association of certain brands of full-length rFVIII products with increased risk for inhibitor development.
In total, 1109 previously untreated patients with severe hemophilia A were treated between 1993 and 2013. A subgroup of 787 patients (the primary analysis cohort) who began treatment in 2004 or later was also assessed.
In the total patient population, 29.0% of patients (322/1109) developed an inhibitor and 17.3% (192/1109) had developed a high‐titer inhibitor. Results from the primary analysis cohort were similar: 29.9% of patients (235/787) developed an inhibitor and 17.2% (135/787) had developed a high‐titer inhibitor.
The combined analysis of the primary cohort revealed a lower risk of high‐titer inhibitor development with the use of third‐generation rFVIII products compared with the use of second‐generation rFVIII products (adjusted hazard ratio, 0.72; 95% CI, 0.49-1.06). Furthermore, the risk for any inhibitor development was significantly lower with the use third‐generation rFVIII products compared with the use of second‐generation rFVIII products.
The investigators found no evidence of a bias due to changing medical practice during the study periods of the 3 previous studies. There were also no baseline imbalances in patient characteristics or rFVIII products among the studies nor any heterogeneity of the results.
The authors called for additional studies on the mechanisms underlying inhibitor development, suggested that “the risk of inhibitor development should be evaluated individually for each medicinal product,” and concluded that “extrapolation of the risk for inhibitor development from one rFVIII product to other recombinant products might not be justified.”
1. Volkers P, Hanschmann K, Calvez T, et al. Recombinant factor VIII products and inhibitor development in previously untreated patients with severe haemophilia A: Combined analysis of three studies [published online May 7, 2019]. Haemophilia. doi:10.1111/hae.13747