Abstracts

Rationale: To determine the earliest onset of response and sustainability of response of adjunctive rufinamide therapy in patients with Lennox-Gastaut syndrome (LGS). Methods: An international, randomized, double-blind, placebo-controlled trial of rufinamide in patients with LGS was conducted in 138 patients (rufinamide, n=74; placebo, n=64).1 Eligible patients were aged between 4 and 30 years, on stable doses of 1-3 AEDs, had multiple types of seizures (including tonic-atonic and atypical absence seizures), experienced a minimum of 90 seizures during the 28-day baseline period prior to randomization, and had a recent history of a slow spike-and-wave pattern on EEG. Target dosage of rufinamide was 45 mg/kg/d, titrated over 1-2 weeks. Two of the primary efficacy variables were the percent change in total seizure and tonic-atonic (ie, sum of tonic and atonic) seizure frequency per 28 days for the entire double-blind phase relative to the baseline phase. Postrandomization clinic visits took place at the end of 1, 2, 4, 8, and 12 weeks. For each of the postrandomization clinic visits, percent change in total seizure and tonic-atonic seizure frequency (postrandomization treatment phase compared to baseline) was calculated using the same statistical approach as the core study. Results: Target dosage of 45 mg/kg/d was achieved by 87.8% of rufinamide-treated patients. Of these, 76.9% reached the target dose in approximately 7 days, with the remaining doing so in approximately 14 days. As previously reported, over the entire double-blind treatment phase, the rufinamide adjunctive therapy group had a greater median percentage reduction in total seizure frequency (32.7% vs 11.7%, p=0.0015) and tonic-atonic (“drop attack”) seizure frequency (42.5% vs -1.4%, p<0.0001). The median percent change in total seizure and tonic-atonic seizure frequency during the double-blind phase relative to the baseline phase by treatment group for each postrandomization visit is shown in Table 1. The rufinamide adjunctive therapy group experienced a statistically significant reduction in total and tonic-atonic seizures compared to the placebo group by the end of 1 week of treatment, and the magnitude of the difference increased with each visit. Conclusions: Compared with placebo, rufinamide-treated patients experienced statistically significant reductions in the frequency of both total seizures and tonic-atonic seizures by the end of the first week of treatment, with further improvement noted over succeeding visits. Rufinamide was tolerated as adjunctive treatment for seizures associated with LGS. These results demonstrate that rufinamide provides a rapid onset of action in the adjunctive treatment of seizures associated with LGS, and also suggest sustainability of treatment response.