EMICIZUMAB DOSING IN CHILDREN AND ADULTS WITH HEMOPHILIA A: SIMULATING A USER-FRIENDLY AND COST-EFFICIENT REGIMEN.

Background When emicizumab is dosed according to label, clinicians are obligated to discard or overdose medication due to discrepancies between calculated dose and vial content. The aim of this study was to compose a cost-efficient emicizumab maintenance dosing regimen using Monte Carlo simulation based on vial size, patient friendly intervals and patient characteristics, while striving for similar plasma concentrations as observed in clinical trials. Methods Monte Carlo simulations were used to investigate alternative dosing regimens in patients weighing 3 to 150 kg. Simulated regimens were targeted to achieve median emicizumab plasma concentrations at steady state (Cav,ss) of 40-60 (90% range: 25-95) µg/ml. The cost-efficiency of the alternative dosing regimen was calculated in mg and costs saved per patient per year. Results The developed alternative dosing regimen achieved similar emicizumab Cav,ss levels compared to the registered dosing regimen with a median deviation of less than 2 µg/mL in 78 % of the bodyweight categories. A dose of 60 mg every 3 weeks was advised for children weighing 12-16 kg, while adults weighing 76-85 kg can receive 120 mg emicizumab every week. Compared to the registered weekly dosing of 1.5 mg/kg, alternative dosing saved €35,434 per year in children weighing between 12 and 16 kg. For patients weighing 76-85 kg the median saving was €29,529 (range: €0 - €59,057). Conclusion This alternative maintenance dosing scheme - applicable in patients with hemophilia A receiving emicizumab prophylaxis - reduces financial costs, avoids medication spillage and is patient friendly without loss of efficacy.