Sirolimus did not significantly decrease seizure frequency in children with tuberous sclerosis complex (TSC) and intractable epilepsy, according to data published in Neurology

Researchers attempted to investigate whether mammalian target of rapamycin complex (mTORC1) inhibitors could reduce seizure frequency in children with TSC. The study was not able to include the target total of 30 children due to slow inclusion rate. Twenty-three children with TSC and intractable epilepsy were enrolled and randomized to open-label, add-on sirolimus immediately or after 6 months. Sirolimus was titrated to trough levels of 5-10ng/mL. 

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The study’s primary endpoint was seizure frequency change during the 6th month of treatment. Data from the intent-to-treat analysis showed that sirolimus led to a 41% decrease in seizure frequency (95% CI: -69% to +14%; P=0.11) vs. the standard-care period. Moreover, 14 children who obtained sirolimus target trough levels in the 6th month had a 61% decrease in seizure frequency (95% CI: -86% to +6%; P=0.06). 

Cognitive development did not change, the study authors noted. Also, all study patients experienced adverse events; 5 children discontinued treatment prematurely.

The authors concluded that although they observed a decrease in seizure frequency especially in children reaching target trough levels, they could not demonstrate a significant benefit. The Class III evidence showed that sirolimus did not significantly reduce seizure frequency in these patients; the study lacked the precision to exclude a benefit from sirolimus treatment. Bigger studies or meta-analyses are needed in the future to investigate whether patients with TSC with seizures benefit from mTORC1 inhibition.  

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