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

Laura H. Bukkems; Kathelijn Fischer; Idske Kremer-Hovinga; Anouk A. M. Donners; Karin Fijnvandraat; Roger E. G. Schutgens; Marjon H. Cnossen; Ron A. A. Mathôt

doi:10.1055/a-1499-0030

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2022; 122(02): 208-215
DOI: 10.1055/a-1499-0030

Coagulation and Fibrinolysis

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

Laura H. Bukkems

¹Hospital Pharmacy-Clinical Pharmacology, Amsterdam University Medical Center, The Netherlands

,

Kathelijn Fischer

²Van Creveldkliniek, University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands

,

Idske Kremer-Hovinga

²Van Creveldkliniek, University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands

,

Anouk A. M. Donners

³Department of Clinical Pharmacy, Division of Laboratory, Pharmacy, and Biomedical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands

,

Karin Fijnvandraat

⁴Pediatric Hematology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

,

Roger E. G. Schutgens

⁵Van Creveldkliniek, Center for Benign Hematology, Thrombosis and Hemostasis, UMC Utrecht, Utrecht, The Netherlands

,

Marjon H. Cnossen^*

⁶Department of Pediatric Hematology, Erasmus University Medical Center - Sophia Children's Hospital Rotterdam, Rotterdam, The Netherlands

,

Ron A. A. Mathôt^*

¹Hospital Pharmacy-Clinical Pharmacology, Amsterdam University Medical Center, The Netherlands

› Author Affiliations

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

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Supplementary Material

Supplementary Material