Surgical outcomes in people with hemophilia A taking emicizumab prophylaxis: experience from the HAVEN 1-4 studies.

Many people with hemophilia A (PwHA) undergo surgery in their lifetime, often due to complications of their disease. Emicizumab is the first bispecific monoclonal antibody prophylactic therapy for PwHA, and its efficacy and safety have been previously demonstrated; however, there is a need to build an evidence base on the management of PwHA on emicizumab undergoing surgery. Data from the HAVEN 1-4 phase 3 clinical trials were pooled to provide a summary of all minor and major surgeries in PwHA with or without factor VIII inhibitors who were receiving emicizumab prophylaxis. Overall, 233 surgeries were carried out during the HAVEN 1-4 trials: 215 minor surgeries (including minor dental and joint procedures, central venous access device placement/removal, and endoscopies) in 115 PwHA (64 with FVIII inhibitors), and 18 major surgeries (including arthroplasty and synovectomy) in 18 PwHA (10 with FVIII inhibitors). Peri-operative hemostatic support was at the discretion of the treating physician. Overall, the median (interquartile range [IQR]) age was 33.5 (13.0-49.0) years and the median (IQR) emicizumab exposure time prior to surgery was 278.0 (177.0-431.0) days. Among the 215 minor surgeries, 141 (65.6%) were managed without additional prophylactic factor concentrate and of those, 121 (85.8%) were not associated with a post-operative bleed. The majority (15/18; 83.3%) of major surgeries were managed with additional prophylactic factor concentrate. Twelve (80.0%) of these 15 surgeries were associated with no intra-operative or post-operative bleeds. The data demonstrate that minor and major surgeries can be performed safely in PwHA receiving emicizumab prophylaxis. These trials are registered at www.clinicaltrials.gov as NCT02622321, NCT02795767; NCT02847637, and NCT03020160.