New findings on inhibitor development: from registries to clinical studies

Abstract

The high incidence of inhibitors against factor VIII (FVIII) concentrates in patients with haemophilia A has encouraged debate as to whether product-type plays a role. There is debate in the literature as to whether rFVIII concentrates are associated with a higher incidence of inhibitors compared to pdFVIII products. The management of haemophilia in patients with inhibitors includes on-demand/prophylaxis treatment with bypassing agents, and/or immune tolerance induction (ITI). However, these options create an economic and emotional burden on patients, their families and healthcare practitioners. Although ITI eliminates inhibitors successfully in 60-80% of cases, it is costly. Despite high costs, preliminary data from a decision analytical model have indicated that ITI is economically advantageous compared with on-demand/prophylactic treatment with bypassing agents. In patients with persistent inhibitors and those who are not candidates for ITI or have failed ITI, bleeding-related mortality and morbidity increase and quality of life decreases, compared with non-inhibitor patients. This article provides an update on the risk of inhibitor development and discusses best management approaches for patients with high-risk factors for inhibitor development.

Keywords: factor VIII; factor concentrate; haemophilia A; inhibitor burden; inhibitor development; previously untreated patients.