Hospital Pharmacy-Clinical Pharmacology, Amsterdam University Medical Center, The Netherlands.
Van Creveldkliniek, University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands.
Thromb Haemost. 2022 Feb;122(2):208-215. doi: 10.1055/a-1499-0030. Epub 2021 Jun 27.
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.
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 ( ) 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.
The developed alternative dosing regimen achieved similar emicizumab 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).
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.
依库珠单抗按标签剂量给药时，由于计算剂量与小瓶含量之间存在差异，临床医生不得不丢弃或过量用药。本研究的目的是基于小瓶大小、患者友好的间隔和患者特征，使用蒙特卡罗模拟制定一种经济高效的依库珠单抗维持剂量方案，同时努力达到临床试验中观察到的相似血浆浓度。
使用蒙特卡罗模拟研究了体重为 3 至 150kg 的患者的替代剂量方案。模拟方案的目标是在稳态（ ）下实现 40 至 60（90%范围：25-95）µg/mL 的依库珠单抗中位血浆浓度。替代剂量方案的成本效益以毫克为单位计算，并计算了每位患者每年节省的成本。
所开发的替代剂量方案与注册剂量方案相比，在 78%的体重类别中实现了相似的依库珠单抗 水平，中位偏差小于 2µg/mL。建议体重为 12 至 16kg 的儿童每 3 周给予 60mg 剂量，而体重为 76 至 85kg 的成年人可以每周给予 120mg 依库珠单抗。与注册的每周 1.5mg/kg 剂量相比，体重为 12 至 16kg 的儿童替代剂量每年可节省 35,434 欧元。对于体重为 76 至 85kg 的患者，中位节省额为 29,529 欧元（范围：0 至 59,057 欧元）。
这种替代维持剂量方案——适用于接受依库珠单抗预防治疗的血友病 A 患者——可降低财务成本，避免药物溢出，且患者友好，不会降低疗效。
