Abstracts

Rationale: AED development for the pediatric population is encumbered by challenges inherent in performing clinical trials in children. To expedite the availability of AEDs to this patient population, extrapolation of efficacy results from adult trials in partial-onset seizures (POS) has been proposed as a predictive tool for assessing AED efficacy in children.Methods: Medline/PubMed, EMBASE, and Cochrane library searches (1970 January 2010) were conducted for AED efficacy trials in the treatment of POS and primary generalized tonic-clonic seizures (PGTCS). Separate searches and algorithms for the < 2 year and 2 18 year age groups were performed due to such factors as age-related epilepsy syndromes and differences in trial design. Trials were selected by predefined criteria (randomized, double blind, placebo-controlled), and the quality and eligibility were evaluated by independent epidemiologists. Placebo-subtracted effect measures were calculated for the median % reduction in seizure frequency from baseline and for the ?50% responder rate. Forest plots were used to evaluate the relative strength of the effect measures.Results: An initial screen identified 3,250 potential articles for evaluation. Quantitative analyses were conducted for adjunctive therapy trials in POS only as there were too few published trials for monotherapy in POS or for any therapy in PGTCS. Among POS trials with adjunctive therapy in adults and in children 2 18 years, 30 articles met pre-defined criteria for analysis. Forest plots for the 2 effect measures were created for 5 drugs (gabapentin, lamotrigine, levetiracetam, oxcarbazepine, and topiramate) from 6 clinical trials and 8 regimens in children and from 24 clinical trials and 46 regimens in adults. Effect measures were consistent between adult and pediatric trials for each compound. The placebo-subtracted median % seizure reduction between baseline and treatment periods, ranging from 7.0% to 58.6% in adults and from 10.5% to 31.2% in children, was significant for 40/46 and 6/6 regimens, respectively. The ?50% responder rate, ranging from 2.0% to 43.0% in adults and from 3.0% to 26.0% in children, was significant for 37/43 and 5/8 regimens, respectively. Three trials conducted in children < 2 years met evaluation criteria. One trial of levetiracetam showed positive efficacy. Mean placebo-subtracted ?50% responder rate ranged from 22.4% to 34.5% in children < 2 years compared to 19.7% for children 2 < 4 years and 7.1% 32.9% in adult trials of levetiracetam. Median % reduction in seizure frequency by age group was not reported in this trial. The other 2 trials (lamotrigine and topiramate) showed effects that were not significantly different than placebo.Conclusions: Results of this systematic review support the extrapolation of efficacy results in adults to predict adjunctive treatment response in 2 18 year old children with partial-onset seizures. Supported by UCB