Real-world experience on the tolerability and safety of emicizumab prophylaxis in paediatric patients with severe haemophilia A with and without FVIII inhibitors

Background Emicizumab is a bispecific monoclonal antibody that bridges activated factor (F) IX and FX, and maintains haemostasis in patients with haemophilia A (PwHA). As a novel agent, many questions remain unanswered about the loss of emicizumab efficacy due to anti-drug antibody (ADA) development, the incidence of inhibitor recurrence in previously tolerized patients, and the risk of de novo inhibitor development. Aim To present real-world experience regarding tolerability, side effects, and outcomes of adverse events of emicizumab prophylaxis in paediatric PwHA. Methods Data on tolerability, compliance, adverse events, and laboratory results of paediatric patients receiving emicizumab prophylaxis, treated at the Haemophilia Comprehensive Care Centre, at Birmingham Children's Hospital between March 2018 and June 2021, were collected. Results Our results showed that out of 52 patients, four experienced minor adverse events, two developed headaches, one developed abdominal pain and nausea, and one developed injection site reactions. Moreover, four patients experienced major adverse events, including severe headaches, major bleeding events, development of ADAs, and recurrence of inhibitors. Emicizumab prophylaxis was discontinued in three patients (5.7% of the cohort) due to adverse events. In addition, emicizumab was discontinued in one patient because of poor compliance. No adverse events were reported in previously untreated/minimally treated patients, represented by four patients in our cohort. Conclusions The real-world experience of emicizumab prophylaxis in our cohort showed that emicizumab was safe and well tolerated in paediatric PwHA with and without inhibitors. Long-term assessment is crucial to monitor major adverse events, recurrence of inhibitors, and development of ADAs.