Anouk Donners

124 Chapter 7 ABSTRACT Introduction Prophylaxis with emicizumab provides effective bleeding protection in persons with haemophilia A (PwHA) but pressures healthcare budgets. The body-weight adjusted dosing at 7-, 14- or 28-day intervals, according to the label, often mismatches the vial content. Entire-vial dosing resulted in therapeutic concentrations according to pharmacokinetic simulations and was introduced to avoid waste. The aim was to evaluate the efficacy of entire-vial dosing of emicizumab by investigating real-world evidence of plasma concentrations, bleeds and drug waste. Methods Single-center, observational study with PwHA receiving emicizumab in mg/kg doses according to label but dosing interval extrapolated to nearest vial size. Patient characteristics and bleeds were compared one year before starting emicizumab, and during emicizumab until January 2022. Concentrations were assessed at Weeks 4, 12, and annually. The mean (95%-confidence interval [CI]) annualized bleed rates (ABR) were compared using negative binomial regression. Drug waste between label-based dosing and entire-vial dosing was compared. Results A total of 112 individuals (94% severe phenotype and 9% positive FVIII inhibitors) were followed for a median of 56 (interquartile range [IQR] 52−68) weeks before and 51 (IQR 29−75) weeks after starting emicizumab. The median emicizumab dose was 5.9 (IQR 5.5–6.2) mg/kg/4 weeks with median concentrations of 63 (IQR 51−80) µg/mL. The ABR of treated bleeds before emicizumab was 3.6 (95%-CI 2.9–4.4) and was 0.8 (95%-CI 0.6–1.1) during emicizumab (p-value < 0.001). Drug waste was reduced by 9%. Conclusion The entire-vial dosing of emicizumab is an attractive treatment option for PwHA leading to therapeutic plasma concentrations, good bleeding control and drug waste avoidance.