Emicizumab

Immune tolerance induction (ITI) remains the only proven strategy for eradicating factor VIII (FVIII) inhibitors in severe hemophilia A, yet low-dose regimens are associated with prolonged treatment and significant bleeding. Emicizumab provides FVIII-independent hemostatic protection and may permit antigen exposure under conditions of reduced bleeding and inflammation during ITI. We conducted a single-center cohort study with historical controls to evaluate the impact of emicizumab on low-dose ITI (LD-ITI) outcomes in pediatric patients (aged <14 years) with severe hemophilia A and high-responding inhibitors undergoing their first LD-ITI (50 IU/kg, 3× per week). Twenty-three patients were included. Patients treated with LD-ITI alone (2010-2020; n = 14) were compared with those receiving LD-ITI plus emicizumab prophylaxis (LD-ITI+EMI; 2021-2023; n = 9). Complete ITI success occurred in 7 of 9 patients (78%) of the LD-ITI+EMI cohort vs 5 of 14 patients (36%) of the LD-ITI cohort (P = .09). Median time to tolerance was shorter with emicizumab (9 vs 19 months; P = .003). Time-to-event analysis confirmed faster tolerance with emicizumab (hazard ratio of 3.89; P = .02). Treated bleeds during ITI were drastically reduced in the emicizumab cohort (median annualized treated bleeding rate, 0.0 vs 5.1; P < .0001), and a higher bleeding burden was associated with delayed tolerance. No thrombotic complications were observed. Median direct treatment costs were comparable between cohorts. In this pediatric cohort, LD-ITI combined with emicizumab was associated with faster tolerance achievement, bleeding reduction, and no increase in direct costs. These findings suggest that ITI associated with emicizumab may provide a more efficient and clinically manageable approach to inhibitor eradication in pediatric patients.