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

Abstract

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.

Emicizumab state‐of‐the‐art update

“…Beyond the clinical trials, emicizumab safety has been documented in multiple real‐world experiences in patients with and without inhibitors 13–19 . In these studies, the emicizumab safety profile was similar to that seen in clinical trials.…”

“…The real-world experience with emicizumab efficacy is still limited to date, with all published efficacy data showing similar results to those reported in the clinical trials. [15][16][17][27][28][29] However, treatment failure in the absence of anti-emicizumab antibodies has now been reported in a child with recurrent intracranial bleeds. 30 This was not seen during the clinical trial conduct.…”

“…The clinical correlates of emicizumab's PK and pharmacodynamic(PD) profile are demonstrated in the HAVEN study program results 12 and several subsequent real-world evidence data sets. [15][16][17][18]28,[43][44][45] Given at a fixed dose of 1.5 mg/kg weekly (or equivalent dosing for longer time intervals), emicizumab provides robust and consistent protection from bleeding. Additionally, standard clotting assays available to most clinical laboratories are unsuitable for measuring emicizumab or its effect and cannot be used for dose adjustments.…”

Emicizumab in children: bleeding episodes and outcome before and after transition to Emicizumab

“…In 2020, the Society for Thrombosis und Hemostasis (GTH) published a guidance regarding the use of Emicizumab that stated a 92% agreement rate to the statement that "The decision to use Emicizumab in small children, especially PUPs, has to be made on an individual base" [15]. Published studies of pediatric patients on Emicizumab included three PUPs and one minimally treated patient in a total cohort of 52 individuals [14] and one PUP in the HOHOEMI study [13]. Both studies reported no other safety pro les or differences in e cacy compared to the other pediatric studies.…”

“…All studies con rmed safety and e cacy of Emicizumab [3], [5]- [7]. Only single other studies have since investigated pediatric patients under prophylaxis with Emicizumab [8]- [12], especially data on previously untreated patients (PUPs) and minimally treated patients (MTPs) [13], [14] are limited.…”