Emicizumab Dosing in Children and Adults with Hemophilia A: Simulating a User-Friendly and Cost-Efficient Regimen

Abstract

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 a steady state (C _av,ss) of 40 to 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 C _av,ss levels compared with the registered dosing regimen with a median deviation of less than 2 µg/mL in 78% of the body-weight categories. A dose of 60 mg every 3 weeks was advised for children weighing 12 to 16 kg, while adults weighing 76 to 85 kg can receive 120 mg emicizumab every week. Compared with 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 to 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.

Keywords

hemophilia A - emicizumab - dose - costs - pharmacokinetics

Author Contributions

L.H.B. and R.A.A.M. performed the analysis and wrote the manuscript. K.Fisher, I.K.-H., and R.E.G.S. proposed the idea of changing the dosing interval proportional to the dose increase. K.Fisher, I.K.-H, A.A.M.D., K. Fijnvandraat, and M.H.C. gave clinical input. K.Fisher, M.H.C., and R.A.A.M. supervised the study. All authors contributed substantially to the critical revision of the manuscript and approved the final draft.

Note

This study was performed as part of the OPTI-CLOT international multicenter research consortium, “Patient tailOred PharmacokineTIc‐guided dosing of CLOTting factor concentrates and desmopressin in bleeding disorders,” which is currently WP6 within the SYMPHONY consortium.

^* Both are last authors.

Publication History

Received: 16 March 2021

Accepted: 03 May 2021

Accepted Manuscript online:
04 May 2021

Article published online:
25 June 2021

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