Key questions in the new hemophilia era: update on concomitant use of FVIII and emicizumab in hemophilia A patients with inhibitors

Authors: Carcao, M., Mancuso, M. E., Young, G., and Jiménez-Yuste, V.

Publication: Expert. Rev. Hematol.; 1-6. February 2021

Affiliations: Division of Haematology/Oncology and Child Health Evaluative Sciences, Research Institute, Hospital for Sick Children, Toronto, Canada; Center for Thrombosis and Hemorrhagic Diseases, Humanitas Clinical and Research Center – IRCCS, Rozzano, Milan, Italy; Children’s Hospital Los Angeles, Los Angeles, University of Southern California Keck School of Medicine, CA, USA; Haematology Department, Hospital Universitario La Paz, Autónoma University, Madrid, Spain

Abstract: INTRODUCTION: Immune tolerance induction (ITI) is the primary therapeutic strategy and only proven method to eradicate inhibitors to coagulation factor VIII (FVIII) in hemophilia A. Emicizumab, a humanized bispecific monoclonal antibody that mimics the function of activated FVIII, has expanded options to treat hemophilia A. The availability of emicizumab necessitates a revisit of recommendations for managing patients with inhibitors. AREAS COVERED: Current evidence is reviewed about the concomitant use of emicizumab and FVIII concentrates during and after ITI. Areas where data are lacking are highlighted and ongoing studies designed to address these issues are described. EXPERT OPINION: Inhibitor eradication remains a desirable goal. All patients with inhibitors should be offered at least one attempt at ITI. Emicizumab monotherapy is an option for inhibitor patients who are not candidates for ITI. Evidence is emerging about the use of emicizumab during ITI to prevent bleeds. Studies are currently addressing the safety, efficacy, and feasibility of concomitant emicizumab and FVIII in ITI. As evidence regarding the risk of inhibitor recurrence and need for continued FVIII to maintain immune tolerance post-ITI is limited, the role of emicizumab alone or in combination with FVIII after ITI is the subject of an upcoming study.