Northwestern University Feinberg Medical School, Chicago, Illinois.
Celgene Corporation, Summit, New Jersey.
J Am Acad Dermatol. 2020 Feb;82(2):389-397. doi: 10.1016/j.jaad.2019.08.019. Epub 2019 Aug 10.
No oral systemic treatments are approved for pediatric patients with psoriasis.
To evaluate the pharmacokinetics and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in pediatric patients with psoriasis.
This phase 2, multicenter, open-label study enrolled pediatric patients with moderate to severe plaque psoriasis. Patients received apremilast twice daily without titration for 2 weeks (group 1 [age, 12-17 years; weight, ≥35 kg]: apremilast 20 or 30 mg; group 2 [age, 6-11 years; weight, ≥15 kg]: apremilast 20 mg), followed by a 48-week extension. Primary endpoints were pharmacokinetics and safety. Other endpoints were taste/acceptability and change from baseline in score on the Psoriasis Area and Severity Index.
A total of 42 enrolled patients (21 adolescents [age, 12-17 years] and 21 children [age, 6-11 years]) received apremilast. Pharmacokinetics modeling and noncompartmental analyses showed that weight-based dosing with apremilast 20 mg twice daily in children or apremilast 20 or 30 mg twice daily in adolescents provides exposure (area under the concentration-time curve from time 0 to 12 hours after the dose) that is comparable to that achieved with apremilast 30 mg twice daily in adults. The safety profile was generally similar to that in adults. Most study participants liked the taste of the tablet. Improvements from baseline in mean Psoriasis Area and Severity Index score were 68% for adolescents (overall) and 79% for children.
No children weighing less than 20 kg were enrolled.
This first-time-in-children phase 2 study supports weight-based apremilast dosing for future phase 3 studies of pediatric plaque psoriasis.
目前尚无获批用于儿童银屑病的口服系统疗法。
评估阿普司特（一种口服磷酸二酯酶 4 抑制剂）在银屑病儿童患者中的药代动力学和安全性。
这项 2 期、多中心、开放标签研究纳入了中重度斑块状银屑病儿童患者。患者连续 2 周（1 组[年龄 12-17 岁；体重 ≥35kg]：阿普司特 20 或 30mg；2 组[年龄 6-11 岁；体重 ≥15kg]：阿普司特 20mg）每日 2 次给药，无需滴定，随后进行 48 周扩展。主要终点为药代动力学和安全性。其他终点包括味觉/可接受性以及从基线起的银屑病面积和严重程度指数评分变化。
共纳入 42 例患者（21 例青少年[年龄 12-17 岁]和 21 例儿童[年龄 6-11 岁]）接受了阿普司特治疗。药代动力学模型和非房室分析显示，在儿童中，阿普司特 20mg 每日 2 次基于体重的给药，或在青少年中，阿普司特 20 或 30mg 每日 2 次给药，可提供与阿普司特 30mg 每日 2 次给药在成人中获得的暴露（从给药后 0 小时到 12 小时的浓度-时间曲线下面积）相当。安全性概况总体上与成人相似。大多数研究参与者喜欢片剂的味道。青少年（总体）的平均银屑病面积和严重程度指数评分从基线的改善为 68%，儿童为 79%。
未纳入体重低于 20kg 的儿童。
这项首次在儿童中开展的 2 期研究支持在未来的儿童斑块状银屑病 3 期研究中进行基于体重的阿普司特给药。
