According to a retrospective study published in the European Journal of Pediatric Neurology, everolimus and sirolimus are being increasingly used for the management of tuberous sclerosis complex (TSC)-associated symptoms, with a generally good safety profile.
For the study, a team of international researchers investigated the utilization practices and safety of 2 mTOR inhibitors, everolimus and sirolimus, in pediatric patients with TSC. De-identified patient data from medical records of infants and children <2 years of age with TSC indications were collected for analysis (n=45). Data collected for the analysis included information on reasons for treatment initiation, treatment duration and dosing, treatment response, and adverse events.
Everolimus was used in 87% of patients, whereas 24% of patients were treated with sirolimus. Of the sirolimus-treated patients, approximately 11% were previously treated with everolimus. The most common reasons for mTOR treatment initiation were epilepsy (45%), subependymal giant cell astrocytomas (39%), rhabdomyomas (7%), and other hamartomas (4%). Overall, the average age at treatment initiation was 11.6±7.6 months. Everolimus was frequently started at an earlier age than sirolimus (11.7±7.8 vs 16.1±7.2 months).
Approximately 78% of treated patients experienced ≥1 treatment-related adverse event (AE), with more AEs reported in the everolimus vs sirolimus group (84% vs 63%, respectively; P =.197). The majority of AEs were considered mild or moderate in severity, and no life-threatening or mortality events were reported with either treatment. A total of 5 (11%) patients had a serious AE related to infectious causes, such as pneumonia or severe upper respiratory infections. Treatment was discontinued in 20% of patients because of an AE. In 64% of patients, partial benefit of therapy was reported compared with no improvement or favorable response in 18% of patients.
The retrospective design, as well as the potential for recall bias, represent noticeable limitations of the study.
The study investigators concluded that the use of mTOR inhibitor therapy in these patients “is reasonably well tolerated and suggests that it could safe or reasonable to use in infants in a future prevention study.”
Krueger DA, Capal JK, Curatolo P, et al; for the TSCure Research Group. Short-term safety of mTOR inhibitors in infants and very young children with tuberous sclerosis complex (TSC): Multicentre clinical experience [published online July 4, 2018]. Eur J Paediatr Neurol. doi: 10.1016/j.ejpn.2018.06.007