Universities of Tours and Nantes, INSERM 1246-SPHERE, Tours, France; Department of Dermatology and Reference Center for Rare Diseases and Vascular Malformations, CHRU Tours, Tours, France.
Universities of Tours and Nantes, INSERM 1246-SPHERE, Tours, France; Clinical Investigation Center, INSERM 1415, CHRU Tours, Tours, France.
J Am Acad Dermatol. 2019 Mar;80(3):735-742. doi: 10.1016/j.jaad.2018.10.070.
Systemic mammalian target of rapamycin (mTOR) inhibitors are currently used in many dermatologic indications. Their topical use is recent and poorly codified.
To provide an overview of the topical use of mTOR inhibitors in dermatologic conditions and evaluate their efficacy and safety.
A literature search was performed in January 2017. Reports of all studies investigating the use of topical mTOR inhibitors in any dermatology diseases were included. The exclusion criteria were systemic use and mucosal administration.
We included 40 studies with a total of 262 patients. In all, 11 dermatologic conditions were found, the most frequent being angiofibromas linked to tuberous sclerosis complex (157 patients). Topical mTOR inhibitors were significantly more efficient than placebo for angiofibromas (relative risk, 2.52; 95% confidence interval, 1.27-5.00; I = 0%). The median concentration of sirolimus was 0.1%, with a median treatment duration of 12 weeks. Topical mTOR inhibitors were well tolerated, with only mild or moderate local side effects (mostly irritative) reported. Blood level of sirolimus was not detected in 90% of patients.
High heterogeneity in most studies.
This systematic review supports the efficacy of topical sirolimus for angiofibromas linked to tuberous sclerosis complex, with only local side effects reported. Other indications require further research.
全身性哺乳动物雷帕霉素靶蛋白(mTOR)抑制剂目前用于多种皮肤科适应证。其局部应用是近期出现的,且规范不足。
概述 mTOR 抑制剂在皮肤科疾病中的局部应用,并评估其疗效和安全性。
2017 年 1 月进行了文献检索。纳入所有研究报告,这些报告均调查了 mTOR 抑制剂在任何皮肤科疾病中的局部应用。排除标准为全身应用和黏膜给药。
共纳入 40 项研究,总计 262 例患者。共发现 11 种皮肤科疾病,最常见的是与结节性硬化症相关的血管纤维瘤(157 例)。局部 mTOR 抑制剂对血管纤维瘤的疗效明显优于安慰剂(相对风险,2.52;95%置信区间,1.27-5.00;I 2 = 0%)。西罗莫司的中位数浓度为 0.1%,中位数治疗时间为 12 周。局部 mTOR 抑制剂耐受性良好,仅报告了轻微或中度的局部副作用(主要是刺激性)。90%的患者未检测到西罗莫司的血药浓度。
大多数研究的异质性较高。
这项系统评价支持局部应用西罗莫司治疗与结节性硬化症相关的血管纤维瘤的疗效,仅报告有局部副作用。其他适应证需要进一步研究。