Use of Emicizumab in Patients with Hemophilia a with and without Inhibitors: A Single Center Experience

Emicizumab is a humanized bispecific recombinant monoclonal antibody that binds the enzyme factor IXa and the substrate factor X and mimics the function of FVIII. It solved some unmet needs of haemophilia A (HA) treatment, such as regimen (once weekly up to once monthly infusion) and route of administration (subcutaneous). Most importantly, emicizumab reduce bleeding episodes and improved the quality of life of these patients. Emicizumab received FDA approval for prophylaxis in HA patients with inhibitors in November 2017 and for patients without inhibitors in October 2018.The aim of this study is to provide information on treatment with emicizumab in patients with severe haemophilia A with and without inhibitors in terms of efficacy, safety and quality of life. Here we report our experience with 9 patients with severe haemophilia A (5 with inhibitors and 4 without inhibitors) that were switched from replacement therapy to emicizumab prophylaxis. Median age at initiation of treatment was 26.8 years for patients with inhibitors and 18.7 years for those without inhibitors. Median duration of therapy was 12 months for patients with inhibitors and 8 months for those without inhibitors. All patients were started on emicizumab with a loading dose of 3 mg/kg once weekly for 4 weeks followed by a maintenance dose of 1.5 mg/kg once weekly or every two weeks. The mean annual bleeding rates (ABR) in patients without inhibitor prior to emicizumab was 1.5 compared to 0 while on emicizumab prophylaxis. In subjects with inhibitors ABR was 1.8 compared to 0.4 while on emicizumab prophylaxis. Furthermore, no adverse events including thrombotic events occurred in course of emicizumab prophylaxis. Bleeding events in course of emicizumab prophylaxis did not request any treatment with replacement therapy or bypassing agents. The questionnaire evaluating quality of life (HAL v 2.0 - 2015 ITA; pedHAL v 2.0 - 2015 ITA) was administered to the patients before switch to emicizumab and after a follow up of six months. The scores showed a significant improvement in terms of quality of life in course of emicizumab prophylaxis. In conclusion, our experience suggests that emicizumab prophylaxis is safe and improved protection against bleeding and quality of life compared to replacement therapy in patients with severe A haemophilia.