Radboud university medical center, Radboud Institute for Health Sciences, Department of Pharmacy, Nijmegen, The Netherlands (Dr Heine).
Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands (Dr Rongen and Rutten).
J Clin Lipidol. 2023 May-Jun;17(3):401-405. doi: 10.1016/j.jacl.2023.03.004. Epub 2023 Mar 15.
Evinacumab is a first-in-class inhibitor of angiopoietin-like protein 3 (ANGPTL3) for treatment of the rare disease homozygous familial hypercholesterolemia (HoFH). With projected drug costs of $450,000 per person per year, the question rises if cost-efficacy of evinacumab can be further improved.
To develop an individualized dosing regimen te reduce drug expenses.
Using the clinical and pharmacological data as provided by the license holder, we developed an alternative dosing regimen in silico based on the principles of reduction of wastage by dosing based on weight bands rather than a linear milligram per kilogram body weight (mg/kg) dosing regimen, as well as dose individualization guided by low density lipoprotein cholesterol (LDL-C) response.
We found that the average quantity of drug used for a dose could be reduced by 34% without predicted loss in efficacy (LDL-C reduction 24 weeks after treatment initiation).
Dose reductions without compromising efficacy seem feasible. We call for implementation and prospective evaluation of this strategy to reduce treatment costs of HoFH.
依维莫司是一种针对血管生成素样蛋白 3（ANGPTL3）的首创抑制剂，用于治疗罕见疾病家族性高胆固醇血症（HoFH）。预计每人每年的药物费用为 45 万美元，因此出现了一个问题，即依维莫司的成本效益是否可以进一步提高。
制定个体化剂量方案以降低药物费用。
利用许可持有人提供的临床和药理学数据，我们根据基于体重分组而非线性毫克/公斤体重（mg/kg）剂量方案进行剂量以减少浪费的原则，以及基于低密度脂蛋白胆固醇（LDL-C）反应的个体化剂量方案，在计算机中开发了一种替代剂量方案。
我们发现，在不预测疗效降低的情况下（治疗开始后 24 周 LDL-C 降低），每个剂量的药物使用量平均可减少 34%。
在不影响疗效的情况下减少剂量似乎是可行的。我们呼吁实施和前瞻性评估这种策略，以降低 HoFH 的治疗成本。
