A retrospective analysis of the efficacy and tolerability of treatment with everolimus in treatment-refractory epilepsy associated with tuberous sclerosis

Rationale: Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disorder characterized by multiple multi-organ hamartomas. Medically refractory epilepsy (MRE) occurs in up to 60% of TSC patients. The results of the EXIST-3 study have shown the efficacy of MRE treatment with an mTOR inhibitor everolimus. In the Russian Federation, the drug has been approved since 2017 for the treatment of TSC-associated MRE in patients above 2 years of age. Aim: To assess the efficacy of everolimus for treatment of medically refractory seizures associated with TSC. Materials and methods: We retrospectively analyzed medical files from 89 patients with TSC who had been admitted with MRE to the Department of Psychoneurology and Epileptology, Research and Clinical Institute for Pediatrics (Moscow, Russia) from November 2016 to December 2018. The patients were divided into three groups depending on their indications for everolimus: 1) 17 patients received with MRE; 2) 64 patients with MRE and subependymal giant cell astrocytoma (SEGA) of > 1 cm in diameter; 3) 8 patients with MRE and renal angiomyolipoma (AML) of > 3 cm in diameter. Their median age was 7.9 year (range, from 2 to 34 years). There were 45 (50.6%) male and 44 (49.4%) female patients. Their treatment lasted from 6 months to 5 years; the dose of everolimus was 8 mg/m² . Focal seizures were more prevalent than epileptic spasms: 60 (67.4%) and 29 (32.6%) patients, respectively. Results: There were 9/17 (52.9%) responders in the MRE group, 16/64 (25%) in the MRE + SEGA group, and 4/8 (50%) in the MRE + AML group. Mild to moderate stomatitis was the most frequent side effect (40.5%). Conclusion: Everolimus is a new important agent for MRE in TSC patients. Treatment with everolimus is safe and well tolerated.