Efficacy and safety of mTOR inhibitors (rapamycin and its analogues) for tuberous sclerosis complex: a meta-analysis
Open accessAbstract
BACKGROUND: 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. METHODS: 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inception to November 2017; the Chinese Food and Drug Administration and clinicaltrials.gov were also searched for unpublished studies.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. RESULTS: 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). CONCLUSION: 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.
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Rapamycin has been extensively utilized for transplant rejection prophylaxis and graft-versus-host disease, as well as seizure control and reduction of tumors in tuberous sclerosis complex patients.
“Rapamycin has been extensively utilized for transplant rejection prophylaxis and graft-versus-host disease, as well as seizure control and reduction of tumors in tuberous sclerosis complex patients [499–501].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [499]
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- Authors
- Li, M., Zhou, Y., Chen, C., Yang, T., Zhou, S., Chen, S., Wu, Y., & Cui, Y.
- Affiliations
- Peking University (CN)
- Peking University First Hospital (CN)
- Corresponding author
- Cui, Yimin
- Venue
- Orphanet Journal of Rare Diseases
- Published
- 2019-02-13
- Volume
- 14
- Issue
- 1
- Pages
- 39-39
- ISSN
- 1750-1172 (ISSN-L)
- PMC
- PMC6373010
- OpenAlex
- W2922550783
- Cited by
- 83
- References
- 38
- Citations by year
- 2026: 8 · 2025: 5 · 2024: 6 · 2023: 16 · 2022: 16 · 2021: 20 · 2020: 11 · 2019: 1
- FWCI
- 1.41
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Orphanet Journal of Rare Diseases (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Development Center for Medical Science and Technology, National Health and Family Planning Commission of the People’s Republic of China (2018ZX09721003-008)
- Topics
- Health Sciences › Medicine › Physiology › Tuberous Sclerosis Complex Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Keywords
- tuberous sclerosis complex, mTOR inhibitors, rapamycin analogs, angiomyolipoma, subependymal giant cell astrocytoma, seizure frequency, tumor response, stomatitis, adverse events, drug safety, drug efficacy, pediatric neurology, epilepsy, seizure frequency reduction
- MeSH terms
- Humans, Tuberous Sclerosis, Sirolimus, TOR Serine-Threonine Kinases
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