Anouk Donners

137 Entire-vial dosing of emicizumab The limitations of this study are typical to those of most retrospective observational studies, although prospectively registered data were used. For instance, ethnicity was not available as determinant in analysis. A limitation might be that the bleed rates that we calculated during emicizumab in this study were overestimated. Selection bias might have been introduced because the need to start emicizumab prophylaxis quickly could have been higher in PwHA with insufficient bleeding control on previous therapy, which could have led to more bleeds for the early switchers in comparison to the later switchers. To overcome this effect, state-of-the-art bleed modelling was performed using a negative binomial regression to account for some of the channelling effects (skewness of bleed data) [21], although long-term data will be more accurate on bleeds during emicizumab. Furthermore, the bleed rates might have been overestimated as some PwHA experience pain and start episodic treatment immediately without an actual bleed occurring [22], and not all of the bleeds were verified by a clinician or were confirmed by imaging. Nevertheless, all the included bleeds were treated with FVIII/BPA. This is relevant from a financial perspective regardless of whether the bleed occurred. Therefore, this study does reflect the real-world setting after emicizumab’s market entry. For future research, we recommend investigating the role of the cost-efficient monitoring of emicizumab. Firstly, the effectiveness plateau was set at >30 µg/mL, while the majority of PwHA in this study (81%) had concentrations of >40 µg/mL. Secondly, similar bleed rates were demonstrated in this study across the concentration subgroups of <40, 40−80 and >80 µg/mL. These two study findings suggest a highly variable dose–response relationship. When considered in this context, entire-vial dosing seems non-controversial and a more liberal dose range might be considered to allow whole-weekly intervals, without the need for monitoring emicizumab concentrations. Furthermore, these two study findings support dosing lower than 6mg/kg/4 weeks (or an equivalent mg/kg with shorter intervals) in a substantial proportion of PwHA. An intervention study is needed to confirm this hypothesis. In conclusion, we evaluated the efficacy of entire-vial dosing of emicizumab in a large Dutch cohort of PwHA and observed therapeutic plasma emicizumab concentrations, good bleeding control and a 9% reduction of drug waste. This real-world evidence supports entire-vial dosing as an attractive and practical option for clinicians who treat PwHA with emicizumab therapy. Author’s contribution AD designed the study, performed data management, conducted data curation, analysis, and validation, 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. 7