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. Mathot*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)


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,sslevels 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.

Original languageEnglish
Pages (from-to)208-215
Number of pages8
JournalThrombosis and Haemostasis
Issue number2
Early online date4 May 2021
Publication statusPublished - 25 Jun 2021

Bibliographical note

Funding Information:
K.Fischer has received speaker’s fees from Bayer, Baxter/Shire, Sobi/Biogen, CSL Behring, Octapharma, Pfizer, and Novo Nordisk, and has performed consultancy for Bayer, Baxter, Biogen, CSL Behring, Freeline, Novo Nordisk, Pfizer, Roche, and Sobi. She and/or her institution has received research support from Bayer, Pfizer, Baxter/Shire, and Novo Nordisk. The institution of K. Fijnvandraat has received unrestricted research grants from CSL Behring, Bayer, Sobi, and Novo Nordisk, and her institution has received consultancy fees from Shire, Roche, Novo Nordisk, and Bayer. M.H.C. has received investigator-initiated research grants over the years from the Netherlands Organization for Scientific Research (NWO), the Netherlands Organization for Health Research and Development (ZonMw), the Dutch “Innovatiefonds Zorgverzekeraars,” Baxter/Baxalta/Shire, Pfizer, Bayer Schering Pharma, CSL Behring, Sobi, Biogen, Novo Nordisk, Novartis, and Nordic Pharma, and has served as a steering board member for Roche and Bayer. All grants, awards, and fees go to the Erasmus MC as institution. R.A.A.M. reports grants from Bayer, grants from Shire, grants from Merck Sharpe Dome, grants from CSL Behring, other from Bayer, other from Shire, outside the submitted work. The remaining authors declare no competing financial interests. All unrestricted research grants, awards, educational grants, and consultancy fees have been forwarded to the respective institutions.

Funding Information:
L.H.B. is funded by the SYMPHONY consortium. The SYMPHONY consortium aims to orchestrate personalized treatment in patients with bleeding disorders, and is a unique collaboration between patients, health care professionals, and translational and fundamental researchers specialized in inherited bleeding disorders, as well as experts from multiple disciplines. It aims to identify best treatment choice for each individual based on bleeding phenotype. In order to achieve this goal, work packages have been organized according to three themes, e.g., Diagnostics (workpackages 3 and 4); Treatment (work-packages 5–9), and Fundamental Research (workpackages 10–12). This research received funding from the Netherlands Organization for Scientific Research (NWO) in the framework of the NWA-ORC Call grant agreement NWA.1160.18.038. Principal investigator: Dr. M.H. Cnos-sen; project coordinator: Dr. S.H. Reitsma. Beneficiaries of the SYMPHONY consortium: Erasmus University Medical Center-Sophia Children’s Hospital, project leadership and coordination; Sanquin Diagnostics; Sanquin Research; Amsterdam University Medical Centers; University Medical Center Groningen; University Medical Center Utrecht; Leiden University Medical Center; Radboud University Medical Center; Netherlands Society of Hemophilia Patients(NVHP); Netherlands Society for Thrombosis and Hemostasis (NVTH); Bayer B.V., CSL Behring B.V., Swedish Orphan Biovitrum (Belgium) BVBA/SPRL.

Publisher Copyright:
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