Egami Akemi, Takahashi Shinji, Kokubo Takeshi, Boggarapu Sreedevi, Beresford Eric
Nobelpharma Co., Ltd., Tokyo, Japan.
Nobelpharma America LLC., Bethesda, MD, 20814, USA.
Dermatol Ther (Heidelb). 2023 May;13(5):1113-1126. doi: 10.1007/s13555-023-00914-2. Epub 2023 Mar 11.
Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disorder affecting several organs, including skin. We sought to assess the real-world effectiveness and safety of a topical sirolimus 0.2% gel treatment for TSC-related cutaneous manifestations.
We conducted an interim analysis of postmarketing surveillance conducted in Japan over 52 weeks. A total of 635 and 630 patients were included in the safety and efficacy analysis sets, respectively. Improvement rate of overall cutaneous manifestations, responder rate of improvement in individual lesions, adverse events (AEs), adverse drug reactions (ADRs), and patient satisfaction level of topical sirolimus 0.2% gel treatment were evaluated along with patient characteristics associated with the improvement rate of cutaneous manifestations or safety.
The mean age of the patients was 22.9 years and 46.1% were men. At week 52 of treatment, the overall improvement rate was 74.8% and the responder rate was the highest for facial angiofibroma (86.2%). Overall, the incidence rates of AEs and ADRs were 24.6% and 18.4%, respectively. Efficacy was associated with age (< 15, ≥ 15 to < 65, and ≥ 65 years, p = 0.010), duration of use (p < 0.001), and total dosage (p = 0.005). Safety was associated with age (< 15, ≥ 15 to < 65, and ≥ 65 years, p = 0.011) and duration of use (p < 0.001). However, when the broad age group (≥ 15 to < 65) was subcategorized by 10-year intervals, the incidence of ADRs was similar among the age groups with no significant differences. Hepatic or renal impairment or concomitant use of systemic mTOR inhibitors had no effect on the effectiveness or safety. Overall, 53% of patients were "very satisfied" or "satisfied" with the treatment received.
Topical sirolimus 0.2% gel is effective in the management of TSC-related cutaneous manifestations and generally well tolerated. Age and duration of usage had a significant association with the effectiveness or safety of topical sirolimus 0.2% gel, whereas total dosage had a significant association with the effectiveness.
结节性硬化症（TSC）是一种罕见的常染色体显性遗传病，会影响包括皮肤在内的多个器官。我们旨在评估0.2%西罗莫司外用凝胶治疗TSC相关皮肤表现的真实疗效和安全性。
我们对在日本进行的为期52周的上市后监测进行了中期分析。安全性分析集和疗效分析集分别纳入了635例和630例患者。评估了0.2%西罗莫司外用凝胶治疗的总体皮肤表现改善率、单个皮损改善的应答率、不良事件（AE）、药物不良反应（ADR）以及患者满意度，同时评估了与皮肤表现改善率或安全性相关的患者特征。
患者的平均年龄为22.9岁，男性占46.1%。在治疗第52周时，总体改善率为74.8%，面部血管纤维瘤的应答率最高（86.2%）。总体而言，AE和ADR的发生率分别为24.6%和18.4%。疗效与年龄（<15岁、≥15至<65岁、≥65岁，p = 0.010）、使用时长（p < 0.001）和总剂量（p = 0.005）相关。安全性与年龄（<15岁、≥15至<65岁、≥65岁，p = 0.011）和使用时长（p < 0.001）相关。然而，当将宽泛年龄组（≥15至<65岁）按10年间隔进行细分时，各年龄组间ADR发生率相似，无显著差异。肝或肾功能损害或同时使用全身性mTOR抑制剂对疗效或安全性无影响。总体而言，53%的患者对所接受的治疗“非常满意”或“满意”。
0.2%西罗莫司外用凝胶对TSC相关皮肤表现的治疗有效，且总体耐受性良好。年龄和使用时长与0.2%西罗莫司外用凝胶的疗效或安全性显著相关，而总剂量与疗效显著相关。
