Abstracts

Because of rapid and significant developmental changes in infants, therapeutic effect of anti-epileptic drugs (AEDs) on seizure frequency is difficult to demonstrate with confidence. A recently completed study (LAM20006) evaluated the safety and efficacy of lamotrigine (LTG) as adjunctive therapy for partial seizures in infants. Data from that study are presented that may help gauge the magnitude of drug effect required to give confidence that true therapeutic benefit is attained. The study had an open-label, adjunctive, optimization phase (OLP) where LTG was added to 1-2 ongoing background AEDs and titrated to optimal clinical benefit. Subjects with a [underline][gt][/underline]40% reduction in partial seizure frequency at optimization were eligible for randomization to an 8-week Double-Blind Phase (DBP), where LTG was either continued or withdrawn over 3 weeks. The primary efficacy endpoint, the number of treatment failures (escapes plus dropouts), was compared using a one-sided Fisher[apos]s exact test with a mid-p correction. In a post-hoc analysis, the proportion of subjects meeting predefined escape criteria was evaluated based on seizure reduction during the OLP optimization. The following groups were analyzed: [underline][gt][/underline]80%, [underline][gt][/underline]70%, [underline][gt][/underline]60%, [underline][gt][/underline]50% and [underline][gt][/underline]40% reduction in seizures during optimization. The proportion of subjects meeting escape criteria, sorted by OLP response, is shown in the following table.[table1]The failure proportion in the placebo group was uniformly high across all OLP response groups indicating that the withdrawal of LTG had a significant impact on seizure occurrence. Subjects who had at least a 40% reduction in seizures during the OLP were statistically more likely to meet escape criteria (experience seizure worsening) when LTG was withdrawn. Efficacy at responses below 40% cannot be ascertained as 40% response in the OLP determined eligibility for randomization. LTG is effective at reducing partial seizures in infants 1-24 months of age. Seizure reductions of at least 40% in the OLP seem to represent the true effects of LTG therapy; however, the evidence is much clearer in the [underline][gt][/underline]50% response subgroup.[table2] (Supported by GlaxoSmithKline.)