Recent treatment strategy for hemophilia A patients who developed inhibitors

Abstract

Hemophilia A is a congenital bleeding disorder caused by genetic abnormalities of the blood coagulation factor (F)VIII. The QOL of hemophilia patients has been markedly improved by the on-demand or prophylactic replacement therapy with clotting factor agents. However, 20–30% of severe hemophilia A patients who received this replacement therapy, develop anti-FVIII alloantibodies (inhibitors). Once this happens, the hemostatic treatment is very uncertain and difficult. Therefore, the inhibitor development is one of the most serious problems. A hemostatic treatment strategy for hemophilia patients who developed inhibitors is to (i) elucidate the risk factor(s) for inhibitor development and prevent this development, (ii) eradicate the inhibitors, and (iii) establish an effective hemostatic and prophylactic treatment. More recently, the outcome of immune-tolerance induction therapy in Japanese hemophilia A patients who developed inhibitors has been reported. Furthermore, a subcutaneous formulation of available bispecific antibody (emicizumab, Hemlibra®) was approved for hemophilia A patients with or without inhibitors. This product decreases markedly the number of bleeding events. I will review the current status of the inhibitor treatment.