Patients with hemophilia A and inhibitors: prevention and evolving treatment paradigms

Authors: Lillicrap, D., Fijnvandraat, K., Young, G., and Mancuso, M. E.

Publication: Expert Rev Hematol ; 1-9. March 2020

Affiliations: Department of Pathology & Molecular Medicine, Queen’s University, Kingston, Canada; Emma Children’s Hospital, Pediatric Hematology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; Hemostasis and Thrombosis Center, Children’s Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA, USA; Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy.

Abstract: INTRODUCTION: Novel non-replacement therapies (e.g. emicizumab) have improved the management of patients with hemophilia A with and without inhibitors while introducing new challenges and increasing the complexity of clinical decision-making. AREAS COVERED: Use of emicizumab can substantially delay initial exposure to FVIII thereby altering the natural history of inhibitor development, but it remains unclear whether later exposure to FVIII might modify the incidence of inhibitor development. Moreover, decisions regarding initiation of immune tolerance induction (ITI) therapy in patients with newly diagnosed inhibitors have become more complicated since emicizumab was introduced. Using emicizumab in lieu of ITI has implications such as precluding the use of FVIII for breakthrough bleeds and surgery, and possibly impacting on patients’ future ability to receive gene therapy. Although bypassing agents are the mainstay of managing acute bleeds and surgery in inhibitor patients, their concomitant use with novel therapies can be difficult to manage/monitor. Evidence from the HAVEN clinical trials program suggests that minor surgeries in inhibitor patients can be performed with emicizumab alone, whereas major surgeries require the use of perioperative bypassing agents. EXPERT OPINION: Until the long-term effects of non-replacement therapies become known, patients who develop inhibitors should continue to receive ITI.