Safety of Sirolimus in Patients with Tuberous Sclerosis Complex under Two Years of Age-A Bicenter Retrospective Study

Background: mTOR inhibitors are a novel pharmacotherapy recommended for subependymal giant astrocytomas, refractory epilepsy, and the treatment of the other clinical manifestations of tuberous sclerosis complex (TSC). Clinical trials on everolimus proved it to be effective and safe in children. Despite its common use in clinical practice, the research on sirolimus is limited. This study is the first to determine and assess the severity of the adverse effects (AEs) of sirolimus administered to children with TSC under two years of age. Methods: We performed a bicenter retrospective data analysis of medical records of individuals with TSC who initiated therapy with sirolimus under the age of two. Results: Twenty-one patients were included in the study. At least one AE was reported in all participants. The most prevalent AEs were anemia, thrombocytosis, and hyperlipidemia. Infections and mouth ulcerations, often reported in the studies on older patients, were infrequent and of mild or moderate grade. Conclusions: Adverse effects associated with sirolimus use in infants and young children with TSC are frequent yet not life- or health-threatening. Further multicenter prospective clinical trials should determine the long-term safety of sirolimus.

Automated summary

This study is the first to determine and assess the severity of adverse effects of sirolimus administered to children under two years of age with TSC. The study found that adverse effects associated with sirolimus use were frequent yet not life- or health-threatening. Further multicenter prospective clinical trials should determine the long-term safety of sirolimus.