Low‐dose immune tolerance induction alone or with immunosuppressants according to prognostic risk factors in Chinese children with hemophilia A inhibitors

Abstract

Abstract Background In developing countries, children with hemophilia A (HA) with high‐titer inhibitor and poor immune tolerance induction (ITI) prognostic risk(s) cannot afford the recommended high‐ or intermediate‐dose ITI. Objectives To determine the efficacy of low‐dose ITI (plasma‐derived factor VIII [FVIII]/von Willebrand factor at 50 FVIII IU/kg every other day) by itself (ITI‐alone) or combined with immunosuppressants rituximab and prednisone (ITI‐IS) in children with HA with high‐titer inhibitor. Methods All enrolled patients had pre‐ITI inhibitor ≥10 BU. We used ITI‐alone if inhibitor titer was <40 BU pre‐ITI and during ITI, and ITI‐IS if titer was ≥100 BU (historic) or ≥40 BU (pre‐ or during ITI) or if the patient was nonresponsive on ITI‐alone. Results Fifty‐six children were analyzable, with median historic peak inhibitor titer 48.0 BU and followed for median 31.4 months. Overall, 35 (62.5%) achieved phase 2 success with negative inhibitor and normal FVIII recovery. The phase 2 success rate was 95% for the 20 patients receiving ITI‐alone. For the 36 patients receiving ITI‐IS, the phase 2 success rate was 44.4%, but would increase to 63.6% if the 14 patients with historic peak inhibitor titer ≥100 BU (and having phase 2 success rate of only 14.3%) were excluded. One patient developed repeated infection after IS treatment. Relapse occurred in 11.4% (4/35) patients with phase 2 success associated with rapid ITI dose reduction or irregular post‐ITI FVIII prophylaxis. Our strategy reduced the cost from high‐dose ITI by 74% to 90%. Conclusion The use of low‐dose ITI with or without immunosuppressants according to ITI prognostic risk(s) is a clinically and economically feasible strategy for eradicating inhibitors in children with HA, particularly for those with historic peak inhibitor titer <100 BU.

Keywords

• hemophilia A
• high‐titer inhibitor
• immune tolerance induction
• low‐dose
• rituximab