Abstracts

Most double-blind, randomized controlled trials of antiepileptic drug (AED) monotherapy in newly diagnosed epilepsy have been conducted in adults; data for children are limited, especially with newer AEDs. A recent dose-comparison study of topiramate (TPM) as monotherapy in untreated epilepsy enrolled patients [ge]6 years of age, thereby providing an opportunity to evaluate the efficacy of TPM as first-line therapy in the subset of children/adolescents with newly diagnosed epilepsy.
Children and adults in whom epilepsy diagnosis had been confirmed [le]3 mos before study entry were eligible provided they had 1 or 2 partial-onset (POS) or primary generalized tonic-clonic (PGTC) seizures in the 3-month retrospective baseline. Patients who had previously achieved seizure remission with AED therapy but relapsed when off AEDs were also eligible. Any AED being used for temporary/emergency purposes was withdrawn during a 7-day open-label phase in which patients received 25 mg/day TPM. Following randomization to double-blind treatment, patients remained in the study until their 1^st POS or GTCS or until 6 months after the last patient was randomized.
Among 470 randomized patients, 151 were children/adolescents ([le]15 yrs), randomized to 50 mg/day TPM (N=74) or 400 mg/day TPM (N=77). Median time since epilepsy diagnosis: 1 month. Median treatment duration: 12 months. Kaplan-Meier analysis for time to 1^st seizure showed a significant (P=0.002) treatment effect favoring TPM 400. The treatment effect emerged within the first week of double-blind treatment and was statistically significant with 100 mg/day TPM. Based on Kaplan-Meier analyses, 6-mo seizure-free rates were: TPM 400, 90%; TPM 50, 78% (P=0.04). 12-mo seizure-free rates: TPM 400, 85%; TPM 50, 62% (P=0.002). Cumulative incidence (up to 2 yrs) for the most common adverse events were headache (21%), upper respiratory infection (17%), appetite decrease (13%), somnolence (12%), weight loss (12%), and dizziness (11%). Of these, only weight loss was dose-related, occurring more frequently in older children (16% of children 12-15 years old vs. 7% of children [lt]12 years old). 9% of children discontinued due to adverse events (TPM 50, 4%; TPM 400, 14%).
Topiramate is the first AED to show, in a randomized double-blind trial, robust treatment effect of monotherapy in children/adolescents with newly diagnosed epilepsy, without exposing patients to the risks of placebo.
[Supported by: Johnson [amp] Johnson Pharmaceutical Research [amp] Development]