Anouk Donners

151 DosEmi study protocol the public disclosure and publication of the research data. The study was registered in the public trial registries of EUDRACT (included in the WHO registry and accepted by all major international medical journals) and the competent authority, prior to inclusion of the first participant. DISCUSSION Individualized dosing of emicizumab based on a target Ctrough of 30 µg/mL is hypothesized to be equally as effective in the prevention of bleeds as conventional dosing. Besides the benefits for participants (i.e., less frequent injections and/or with lower volume), this PK-guided dosing is expected to result in significant healthcare savings and improved cost-effectiveness without loss of bleeding control. The DosEmi Study has enrolled its first participant in September 2022. Our study is supported by several reports on reduced dosing of emicizumab without loss of efficacy. Reported first was a case of a boy in whom higher emicizumab concentrations of ~90 µg/mL were associated with more episodes of pain in muscles and joints [37]. The dose was reduced to result in emicizumab concentrations of ~24 µg/mL, after which the pain resolved and no bleeds occurred during the following six months. Subsequently, emicizumab was given in lower doses in 11 PwHA from Finland and 6 PwHA from Thailand without loss of efficacy [19, 38]. Additionally, real-world evidence from our center demonstrated similar bleed rates across the concentration subgroups of <40 µg/mL (n = 13), 40−80 µg/mL (n = 59) and >80 µg/mL (n = 22) [15]. We assume that, in clinical practice, many others dose emicizumab in a reduced form without publishing the results, especially as global access is limited [39]. There are limitations and strengths to the DosEmi Study. The sample size is relatively large for a rare disorder, requiring a labour-intensive multicenter design. Furthermore, recruitment of paediatric participants may be difficult [40] and potential participants may be reluctant to reduce dosing of an effective treatment. Nevertheless, the study provides a unique opportunity to evaluate alternative dosing strategies in a safe and wellcontrolled clinical setting. Additionally, the opportunity for patients (especially children) to receive fewer painful emicizumab injections is provided. This study can eventually provide meaningful conclusions that benefit the global application of reduced dosing. Author’s contribution AD helped in study design, prepared the first draft of the manuscript, and implemented significant contribution from co-authors up to the final publication. Throughout the process, AD asked and implemented input and feedback from supervision team and co-authors, who performed critical review of the manuscript and provided significant contributions to the study. 8