Department of Pharmacy, Peking University First Hospital, 6 Dahongluochang Street, Xicheng District, Beijing, 100034, China.
Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Science, Peking University, Beijing, China.
Orphanet J Rare Dis. 2019 Feb 13;14(1):39. doi: 10.1186/s13023-019-1012-x.
The treatment of tuberous sclerosis complex (TSC) using mammalian target of rapamycin (mTOR) inhibitors is clinically promising. The aim of the present study was to evaluate the efficacy and safety of mTOR inhibitors for improving the clinical symptoms of TSC.
We performed a systematic search of major electronic databases (PubMed, EMBASE, Cochrane Library and WanFang, CNKI, and VIP databases) to identify randomized controlled trials (RCTs) and quasi-randomized studies from the date of database inception to November 2017; the Chinese Food and Drug Administration and clinicaltrials.gov were also searched for unpublished studies. The endpoints of the study were the tumor response rate and seizure frequency response rate (the proportion of patients achieving a ≥ 50% reduction relative to the baseline). Two researchers screened articles, assessed the risk of bias and extracted data independently. The included RCTs were analyzed using RevMan 5.3, which was provided by the Cochrane Collaboration.
Compared with the placebo, mTOR inhibitors significantly reduced tumor volume in both angiomyolipoma (AML) (RR = 24.69, 95% CI = 3.51,173.41, P = 0.001) and subependymal giant cell astrocytoma (SEGA) (RR = 27.85, 95% CI = 1.74,444.82, P = 0.02). Compared with the placebo, mTOR inhibitors significantly reduced seizure frequency (RR = 2.12, 95% CI = 1.41,3.19, P = 0.0003). Regarding safety, compared with patients who did not receive mTOR inhibitors, those who did had a higher risk of suffering stomatitis (RR = 3.20, 95% CI = 1.49,6.86, P = 0.003). In contrast, patients who did and did not receive mTOR inhibitors experienced similar adverse events, such as upper respiratory tract infections (RR = 1.08, 95% CI = 0.81,1.45, P = 0.59) and nasopharyngitis (RR = 0.86, 95% CI = 0.60,1.21, P = 0.38).
In view of the efficacy and safety associated with tumor and seizure frequency in the TSC patients, mTOR inhibitors is a good therapeutic choice. Unlike the risks of upper respiratory tract infections and nasopharyngitis, mTOR inhibitors seem to increase the risk of stomatitis, mostly grade 1 and 2.
哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂治疗结节性硬化症（TSC）具有临床应用前景。本研究旨在评估 mTOR 抑制剂改善 TSC 临床症状的疗效和安全性。
我们对主要电子数据库（PubMed、EMBASE、Cochrane 图书馆、万方、中国知网和维普数据库）进行了系统检索，以确定从数据库建立到 2017 年 11 月的随机对照试验（RCT）和准随机研究；还检索了中国食品药品监督管理局和临床试验.gov 以获取未发表的研究。该研究的终点是肿瘤反应率和癫痫发作频率反应率（与基线相比，达到≥50%减少的患者比例）。两位研究人员独立筛选文章、评估偏倚风险和提取数据。使用 Cochrane 协作提供的 RevMan 5.3 分析纳入的 RCT。
与安慰剂相比，mTOR 抑制剂可显著降低血管平滑肌脂肪瘤（AML）（RR=24.69，95%CI=3.51，173.41，P=0.001）和室管膜下巨细胞星形细胞瘤（SEGA）（RR=27.85，95%CI=1.74，444.82，P=0.02）的肿瘤体积。与安慰剂相比，mTOR 抑制剂可显著降低癫痫发作频率（RR=2.12，95%CI=1.41，3.19，P=0.0003）。关于安全性，与未接受 mTOR 抑制剂的患者相比，接受 mTOR 抑制剂的患者发生口腔炎的风险更高（RR=3.20，95%CI=1.49，6.86，P=0.003）。相比之下，接受和未接受 mTOR 抑制剂的患者经历了类似的不良反应，如上呼吸道感染（RR=1.08，95%CI=0.81，1.45，P=0.59）和鼻咽炎（RR=0.86，95%CI=0.60，1.21，P=0.38）。
鉴于 TSC 患者的肿瘤和癫痫发作频率与疗效和安全性相关，mTOR 抑制剂是一种较好的治疗选择。与上呼吸道感染和鼻咽炎的风险不同，mTOR 抑制剂似乎会增加口腔炎的风险，主要为 1 级和 2 级。
