Immune tolerance induction in severe haemophilia A: A UKHCDO inhibitor and paediatric working party consensus update

Introduction In good risk patients (historic inhibitor peak < 200BU), the International Immune Tolerance Study demonstrated equal efficacy to induce tolerance between high (200iu/kg/day) and low dose (50iu/kg x3 times/week) immune tolerance induction (ITI) regimens. However, the trial stopped early on account of the excessive bleed rate in the low dose ITI arm. Methods United Kingdom Haemophilia Centre Doctors' Organization (UKHCDO) Paediatric and Inhibitor working parties considered available ITI data alongside the bi-phenotypic antibody emicizumab (Hemlibra (R)) efficacy and safety data to develop a consensus guideline for the future UK ITI guideline. Results This revision of UKHCDO ITI guidance incorporates the recommendation to use emicizumab as a prophylaxis haemostatic agent to reduce bleeding rates and to facilitate low dose and reduced frequency of FVIII CFC for ITI in the majority of children. Conclusion This consensus protocol will facilitate future evaluation of ITI outcomes in the evolving landscape of haemophilia therapeutics and ITI strategies.

Automated summary

The International Immune Tolerance Study showed equal efficacy between high and low dose immune tolerance induction regimens in good risk patients, but was stopped early due to excessive bleed rate in the low dose arm. The UKHCDO guideline revision now recommends using emicizumab as a prophylaxis agent for reduced bleeding rates during ITI. This consensus protocol aims to facilitate future evaluation of ITI outcomes in the changing landscape of haemophilia therapeutics and strategies.