Safety and Efficacy of the Sirolimus Gel for TSC Patients With Facial Skin Lesions in a Long-Term, Open-Label, Extension, Uncontrolled Clinical Trial
Safety and Efficacy of the Sirolimus Gel for TSC Patients With Facial Skin Lesions in a Long-Term, Open-Label, Extension, Uncontrolled Clinical Trial
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DOI：
10.1007/s13555-020-00387-7
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发表时间：
2020-05-08
影响因子：
3.4
通讯作者：
Murota, Hiroyuki
中科院分区：
文献类型：
--
作者：
Wataya-Kaneda, Mari;Nagai, Hiroshi;Murota, Hiroyuki
引言我们以前的临床研究已经证明了西罗莫司凝胶对结节性硬化症（TSC）患者的短期疗效和安全性。然而，缺乏长期的临床证据。我们的目的是评估西罗莫司凝胶长期治疗TSC患者皮肤病变的安全性和有效性。方法我们对94名日本TSC患者进行了一项多中心、开放标签、非对照临床试验。患者将0.2%西罗莫司凝胶每天两次涂抹在面部或头部，持续> 52周（安全性最长136周）。安全性终点为不良事件（AE）导致的停药率（主要终点）和AE发生率。疗效终点为血管纤维瘤、头部斑块和色素减少斑的缓解率。结果94例患者（平均年龄21岁，范围3-53岁）中，AE导致的停药率为2.1%（2/94例）。尽管给药部位刺激和皮肤干燥相对频繁发生，但药物相关AE均不严重;大多数药物相关AE迅速消退。主要药物相关AE（发生率>= 5%）为给药部位刺激（30.9%）、皮肤干燥（27.7%）、痤疮（20.2%）、眼刺激（8.5%）、瘙痒（8.5%）、红斑（7.4%）、痤疮样皮炎（6.4%）和接触性皮炎（5.3%）。血管纤维瘤、头部斑块和色素减少斑的缓解率分别为78.2% [95%置信区间（CI）68.0-86.3%]、66.7%（95% CI 51.1-80.0%）和72.2%（95% CI 46.5-90.3%）。结论该凝胶剂对累及面部皮损的TSC患者耐受性好，持续有效。
Introduction Our previous clinical studies have demonstrated the short-term efficacy and safety of the sirolimus gel for patients with tuberous sclerosis complex (TSC). However, long-term clinical evidence is lacking. Our objective was to assess the safety and efficacy of long-term treatment with the sirolimus gel for the skin lesions of TSC patients. Methods We conducted a multicenter, open-label, uncontrolled clinical trial in 94 Japanese patients with TSC. Patients applied the 0.2% sirolimus gel on their face or head twice daily for > 52 weeks (maximum 136 weeks for safety). The safety endpoints were the rate of adverse event (AE)-caused discontinuation (primary endpoint) and the incidence of AEs. The efficacy endpoint was the response rate of angiofibromas, cephalic plaques, and hypomelanotic macules. Results Among 94 enrolled patients (mean age, 21 years; range 3-53 years), the rate of AE-caused discontinuation was 2.1% (2/94 patients). Although application site irritation and dry skin occurred relatively frequently, none of the drug-related AEs were serious; most of the drug-related AEs resolved rapidly. The major drug-related AEs (>= 5% in incidence) were application site irritation (30.9%), dry skin (27.7%), acne (20.2%), eye irritation (8.5%), pruritus (8.5%), erythema (7.4%), dermatitis acneiform (6.4%), and dermatitis contact (5.3%). The response rates of angiofibromas, cephalic plaques, and hypomelanotic macules were 78.2% [95% confidence interval (CI) 68.0-86.3%], 66.7% (95% CI 51.1-80.0%), and 72.2% (95% CI 46.5-90.3%), respectively. Conclusions The gel was well tolerated for a long time by patients with TSC involving facial skin lesions and continued to be effective.