TSC is an autosomal dominant neurocutaneous syndrome affecting more than 1-1.5 million people worldwide and characterized by tumor formation and neurological symptoms. Everolimus is an oral protein kinase inhibitor of the mTOR serine/threonine kinase signal transduction pathway with antibiotic, antiproliferative, and immunosuppressive actions that may have a role in treating TSC.

We systematically searched four electronic databases; PubMed, Cochrane Library, Scopus, and Web of science for eligible clinical trials. We screened records for eligibility and extracted the data from relevant studies. Continuous data were pooled as mean difference (MD) or standardized mean difference (SMD) and 95% confidence interval (CI), while dichotomous data were pooled as risk ratio (RR) or event rate (ER) and 95% CI.

We included 11 double-arm studies with 721 participants and 27 single-arm studies with 987 participants. Compared with placebo, everolimus increased the proportion of patients with ≥ 50% reduction regarding renal angiomyolipoma (AML) (P=0.001) and skin lesions (P=0.001) with no effect on social dysfunction (P=0.54) or autism (P=0.68). Everolimus also significantly increased the proportion of patients with ≥ 50% of AML at 12, 36, 48, 60 (P=0.05) months, sub ependymal giant cell astrocytoma (SEGA) at 6, 12 (P=0.02) months, epilepsy at 12, 24 (P=0.02) months, and skin lesions at 3, 6, 12 (P=0.0) months.

Everolimus reduces the incidence of SEGA and AML over time, especially in pediatric patients, in addition to skin lesions and seizure frequency.