Division of Pharmacometrics, Office of Clinical Pharmacology, Food and Drug Administration, Silver Spring, Maryland, USA.
CPT Pharmacometrics Syst Pharmacol. 2013 Aug 21;2(8):e67. doi: 10.1038/psp.2013.44.
Fingolimod 0.5 mg q.d. (once daily) has been approved for the treatment of patients with relapsing and remitting forms of multiple sclerosis (RRMS). Fingolimod at two doses (0.5 and 1.25 mg) showed superior effectiveness in the frequency of relapse with little difference between the two dose groups. At the same time, fingolimod manifests a number of dose-dependent adverse events. Given the safety concerns and similar effect size at both dose groups, it was reasonable to raise the question whether doses even lower than 0.5 mg would produce sufficient effectiveness. Therefore, our analysis focused on estimating the effect size of the primary endpoint at doses lower than 0.5 mg via exposure-response analysis. Specifically, we aim to show how biomarker data can be used as a bridge in exposure-response analysis to estimate the clinical endpoint response at certain doses when the direct relationship between exposure and the clinical endpoint can not be quantified reliably.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e67; doi:10.1038/psp.2013.44; published online 21 August 2013.
芬戈莫德 0.5mg，qd（每日一次）已获批准用于治疗复发缓解型多发性硬化症（RRMS）患者。两种剂量（0.5 和 1.25mg）的芬戈莫德在复发频率方面显示出更好的疗效，两组之间差异不大。同时，芬戈莫德表现出许多剂量依赖性不良事件。鉴于安全性问题和两个剂量组之间的效果大小相似，提出一个问题是，即使低于 0.5mg 的剂量是否会产生足够的疗效是合理的。因此，我们的分析重点是通过暴露-反应分析来估计低于 0.5mg 剂量的主要终点的效果大小。具体来说，我们旨在展示如何在暴露-反应分析中使用生物标志物数据作为桥梁，在无法可靠量化暴露与临床终点之间直接关系的情况下，估计特定剂量的临床终点反应。CPT：药物代谢动力学和系统药理学（2013）2，e67；doi：10.1038/psp.2013.44；在线发表于 2013 年 8 月 21 日。
