Emicizumab Prophylaxis in Patients with Hemophilia Α with and without Inhibitors

Background: Hemophilia A is an X-linked congenital bleeding disorder caused by deficient or defective factor VIII (FVIII), characterized by spontaneous or traumatic bleeding into joints, muscles, and body cavities. The burden of disease is high, as prophylaxis for bleed prevention requires several weekly intravenous factor infusions which are expensive and inconvenient. By adulthood, fewer than 50% comply and many develop pain, joint degeneration, and disability. For the 30% who develop inhibitors, requiring bypass therapy, which is associated with poor response, frequent hospitalization, and high cost. The bispecific monoclonal antibody emicizumab is licensed to prevent bleeds in hemophilia A (HA) and HA with inhibitors (HA-I). While it mimics FVIII by bridging FIXa and FX, it differs from FVIII biochemically, with no phospholipid binding and limited self-regulation. Thus, whether bleed frequency and severity, long-term joint health, and quality of life are comparable to FVIII is unknown. Methods: We reviewed outpatient medical records of HA and HA-I cared for at Hemophilia Center of Western Pennsylvania, switched to emicizumab between November 2017 and May 2019. This was an expedited study approved by the University of Pittsburgh IRB, PRO1800098. Means, medians, and standard deviations or frequencies were determined for clinical variables, including age race, genotype, reason for switching, bleeding events, surgical events, and treatment rating. Group comparisons were by Student's t test for continuous data, or chi-square or Fisher's exact test for discrete data. A p-value of Results: A total of 42 patients initiated emicizumab during outpatient comprehensive clinic, including 18 (42.9%) HA and 24 (52.1%) HA-I. Of these, 17 (47.3%) were Discussion: This study indicates the majority of HA and HA-I switching to emicizumab experience low ABR, infrequent surgical bleeding, and subjective improvement in health. Postoperative thrombosis/TMA suggests FEIBA should be avoided for at least 6 months after emicizumab discontinuation, during which it may still be detected. Disclosures Xavier: Bioverativ/Sanofi: Research Funding. Seaman: Takeda: Consultancy; Bayer: Consultancy; Genentech: Consultancy; Spark Therapeutics: Consultancy. Ragni: Alnylam/Sanofi: Other: Advisory Board, Research Funding; BioMarin: Other: Advisory Board, Research Funding; Bioverativ/Sanofi: Other: Advisory Board, Research Funding; OPKO: Research Funding; Sangamo: Research Funding; Shire/Takeda: Other: Advisory Board, Research Funding; Spark Therapeutics: Other: Advisory Board, Research Funding.