An updated meta-analysis of effectiveness and safety of mTOR inhibitors in the management of tuberous sclerosis complex patients.

Abstract

PURPOSE:

Tuberculous sclerosis complex (TSC) is an autosomal dominant multi-system disease. In TSC patients, the inhibition of mTOR pathway is weakened, which leads to the uncontrolled proliferation of normal resting cells. Therefore, mTOR inhibitors have many therapeutic potentials in the treatment of TSC. However, there is no consensus on the safety and efficacy of mTOR inhibitors so far. This article aimed to present new evidence for the efficacy and safety of mTOR inhibitors in the treatment of TSC by evaluating published clinical trials.

METHODS:

A systemic search of online databases, such as Cochrane Library, Embase, PubMed, and the US National Institutes of Health Clinical Trials Registry, was conducted. The researchers selected studies that met the following entry criteria: randomized, double-blinded or single-blinded, placebo-controlled, parallel-group studies with active and control arms receiving rapamycin or everolimus and matched placebo, respectively. The meta-analysis included seven studies. Tumor response or epilepsy seizure frequency response rates were considered efficacy outcomes.

RESULTS:

In seven studies involving 877 patients, using of mTOR inhibitors therapy showed an improvement in both tumor response and seizure frequency outcomes in TSC. In combination of AML (angiomyolipomas), SEGA (subependymal giant cell astrocytoma), epilepsy, and facial angiofibroma subjects, the RR is 3.01 (95% CI 2.03 to 4.45, p = 0.000) with observed heterogeneity (I-squared = 55.4%). The main side effect of mTOR inhibitors was stomatitis.

CONCLUSION:

The updated meta-analysis suggests that the use of mTOR inhibitors is an effective therapy for patients with TSC.

• Authors: Mengling Liu, Jiayou Ye, Xiaoling You
• Journal: Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery (Childs Nerv Syst) (Oct 31 2023) ISSN: 1433-0350 [Electronic] Germany
• PMID: 37906297 (Publication Type: Journal Article)
• Copyright: © 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.