Emicizumab in tolerized patients with hemophilia A with inhibitors: A single-institution pediatric cohort assessing inhibitor status

Background: The majority of patients with hemophilia A with inhibitors who undergo immune tolerance induction (ITI) achieve successful tolerance and transition to factor VIII (FVIII) prophylaxis. A portion of these patients have switched to emicizumab for bleeding prevention. However, the risk of inhibitor relapse on emicizumab is unclear. Objective: To evaluate the inhibitor status of patients with hemophilia A and inhibitors who achieved successful/partial tolerance after ITI and transitioned from FVIII prophylaxis to emicizumab. Methods: This is a single-institution, retrospective review of pediatric patients with severe hemophilia A who have completed ITI with FVIII and switched to emicizumab. Results/Conclusions: Seven successfully tolerized and five partially tolerized patients were identified. Three patients continued intermittent FVIII infusions on emicizumab at 50-70 IU/kg twice weekly, once weekly, or every other week due to concerns for inhibitor relapse or loss of recent FVIII tolerance by the treating provider. Eleven of 12 patients (92%) maintained negative inhibitor titers at a mean follow-up of 14.2 +/- 6.1 months. One individual had an inhibitor relapse with a peak titer of 2.5 BU/mL. Five of the 11 patients (45%) with negative inhibitor titers had detectable nonneutralizing anti-FVIII IgG4 antibodies, but none of the patients had detectable IgG1 antibodies. There were no inhibitor recurrences in a subset of six patients after FVIII re-exposure for bleeding events or surgery. Given that the presence of an inhibitor significantly impacts factor product choice for bleeding management, ongoing inhibitor monitoring in tolerized patients with hemophilia A who transition to emicizumab is strongly recommended.

Automated summary

The majority of hemophilia A patients who undergo ITI successfully achieve tolerance and transition to emicizumab, with most of them maintaining negative inhibitor titers. However, ongoing monitoring of inhibitors and careful selection of factor products are still recommended.