Tokyo Medical University, Tokyo, Japan.
Jichi Medical University, Shimotsuke, Japan.
J Dermatol. 2021 Nov;48(11):1652-1664. doi: 10.1111/1346-8138.16068. Epub 2021 Aug 15.
Apremilast is an orally available phosphodiesterase 4 inhibitor used for the treatment of moderate to severe psoriasis. The aims of this analysis were to develop a population pharmacokinetic (PPK) model of apremilast based on observed data from phase 1 studies combined with clinical trial data from subjects with moderate to severe psoriasis, and to develop exposure-response (E-R) models to determine whether Japanese subjects with moderate to severe psoriasis achieve response to apremilast treatment similar to that observed in non-Japanese, predominantly Caucasian subjects with moderate to severe psoriasis. The PPK model demonstrated that apremilast plasma concentrations and overall apparent clearance rate were comparable between the Japanese and Caucasian subgroups. The E-R analyses of ≥75% or ≥50% improvement from baseline in Psoriasis Area and Severity Index score and achievement of static Physician Global Assessment score of 0 (clear) or 1 (almost clear) at week 16 indicated that apremilast treatment in Japanese subjects approached the maximal effect with response rates comparable to those in predominantly Caucasian subjects. Overall, the analyses confirm that the approved apremilast 30 mg b.i.d. dose is appropriate for Japanese subjects with moderate to severe psoriasis, with an efficacy profile similar to that previously observed in Caucasian subjects.
阿普斯特是一种可口服的磷酸二酯酶 4 抑制剂，用于治疗中度至重度银屑病。本分析旨在基于来自 1 期研究的观察数据和来自中重度银屑病患者的临床试验数据，建立阿普斯特的群体药代动力学（PPK）模型，并建立暴露-反应（E-R）模型，以确定日本中重度银屑病患者对阿普斯特治疗的反应是否与观察到的中重度银屑病的非日本、主要为白种人患者相似。PK 模型表明，阿普斯特的血浆浓度和总体表观清除率在日本和白种人亚组之间是可比的。E-R 分析表明，在第 16 周时，从基线改善≥75%或≥50%的银屑病面积和严重程度指数评分，以及达到静态医生整体评估评分 0（清除）或 1（几乎清除）的患者比例，表明阿普斯特治疗在日本患者中接近最大效应，其反应率与主要为白种人患者相似。总的来说，这些分析证实，批准的阿普斯特 30mg bid 剂量适用于日本中重度银屑病患者，其疗效与先前观察到的白种人患者相似。
