Immune tolerance induction in severe haemophilia A: A UKHCDO inhibitor and paediatric working party consensus update
Daniel P. Hart, Jayanthi Alamelu, Neha Bhatnagar, Tina Biss, Peter W. Collins, Georgina Hall, C. R. M. Hay, Ri Liesner, Michael Makris, Mary Mathias, Jayashree Motwani, Ben Palmer, Jeanette Payne, Charles Percy, Michael Richards, Anne Riddell, Kate Talks, Oliver Tunstall, Elizabeth Chalmers
Abstract
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 ×3 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®) 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.