Anouk Donners

142 Chapter 8 ABSTRACT Introduction Emicizumab effectively prevents bleeding in people with haemophilia A (PwHA), but is a burden for national healthcare budgets and consequently may limit access. According to the drug label, dosing of emicizumab is based on body weight with fixed intervals of 7, 14 or 28 days, which leads to mean plasma concentrations of 55 µg/mL (SD 15 µg/mL). However, a moderate variability of concentrations and a minimal effective concentration of 30 µg/mL have been suggested in studies. Therefore, a dose of emicizumab that targets a trough concentration of 30 µg/mL is hypothesized to be equally effective as conventional dosing in the prevention of bleeding. Methods We designed a phase IV, multicenter, open-label, crossover study to evaluate noninferiority of bleed control of ≥6 months on conventional dosing in comparison to ≥6 months on dose intervention. This dose intervention consists of reducing the dose of emicizumab to target a trough concentrations of 30 µg/mL using individual pharmacokinetic (PK) parameters. Ninety five PwHA aged > 1 years who received conventional dosing of emicizumab for ≥12 months with good bleeding control during the last 6 months will be recruited from all Dutch haemophilia treatment centers. The study is powered to detect a clinically relevant decrease (risk difference) of 15% in the proportion of patients without treated bleeds during both follow-up periods. Secondary endpoints are spontaneous joint- or muscle bleeds, and annualized treated bleeding rates (using negative binomial regression). Cost-effectivity between conventional dosing and individualized PK-guided dosing of emicizumab will be compared. Ethics and dissemination The DosEmi Study was approved by the Medical Ethics Review Committee NedMec of the University Medical Center of Utrecht, the Netherlands. Study results will be communicated through publications in international scientific journals and presentations at (inter)national conferences. Trial registration number: EUCTR2021-004039-10-NL at