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Published on: September 30, 2021
Recombinant factor VIII products and inhibitor development in previously untreated boys with severe hemophilia A
Thierry Calvez1, Hervé Chambost2, Ségolène Claeyssens-Donadel3
1Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Unité Mixte de Recherche en Santé 1136, Institut Pierre Louis d'Épidemiologie et de Santé Publique, Paris, France; INSERM, Unité Mixte de Recherche en Santé 1136, Institut Pierre Louis d'Épidemiologie et de Santé Publique, Paris, France;
Abstract:
Six recombinant factor VIII (rFVIII) products have been marketed worldwide. In 2013, the Research of Determinants of Inhibitor Development (RODIN) study group reported an unexpectedly high risk of inhibitor development with a second-generation full-length rFVIII (Product D) in previously untreated patients (PUPs) with severe hemophilia A (HA). In 1994, French public health authorities established a prospective cohort to monitor hemophilia treatment safety. A PUP subgroup was designed to investigate inhibitor risk factors. We analyzed this subcohort in view of the RODIN findings. After excluding 50 patients who participated in the RODIN study, the primary analysis focused on 303 boys with severe HA first treated with a rFVIII product. A clinically significant inhibitor was detected in 114 boys (37.6%). The inhibitor incidence was higher with Product D vs the most widely used rFVIII product (adjusted hazard ratio [aHR], 1.55; 95% confidence interval [CI], 0.97-2.49). Similar results were found for high-titer inhibitors and in 10 sensitivity analyses. No heterogeneity was observed between RODIN and our results. Combined aHRs were 1.58 (95% CI, 1.17-2.14) for all inhibitors and 1.70 (95% CI, 1.15-2.52) for high-titer inhibitors. Our results confirm the higher immunogenicity of Product D vs other rFVIII products in PUPs with severe HA.
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