Successful immune tolerance induction using efanesoctocog alfa in severe hemophilia A: A case series

The development of neutralizing factor VIII (FVIII) inhibitors remains a major therapeutic challenge in severe hemophilia A. We report two patients with complex inhibitor histories who achieved rapid and sustained inhibitor eradication using efanesoctocog alfa. Immune tolerance induction (ITI) was initiated at 100 units (U)/kg 3 times weekly, with subsequent dose reduction after inhibitor clearance. Inhibitor titers declined to undetectable levels (<0.5 Bethesda units [BU]) within 6 weeks in one case and 3 months in the other, with FVIII recovery exceeding 90%. Transition to once-weekly individualized prophylaxis maintained functional FVIII activity and therapeutic FVIII trough levels (4%-6%), allowing discontinuation of emicizumab. Sustained bleed-free outcomes were achieved with individualized prophylactic dosing without inhibitor recurrence. These cases support efanesoctocog alfa-based ITI as a promising strategy for rescue and retreatment patients with complex inhibitor histories.