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 2 patients with complex inhibitor histories who achieved rapid, sustained inhibitor eradication with efanesoctocog alfa. Immune tolerance induction was initiated at 100 U/kg 3 times weekly, with subsequent dose reduction after inhibitor clearance. Inhibitor titers declined to undetectable levels (<0.5 Bethesda Units) 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 immune tolerance induction as a promising strategy for rescue and retreatment in patients with complex inhibitor histories.