Abstracts

Rationale: The management of epilepsy aims for seizure freedom; however, response to pharmacological treatment varies among patients.1 Poor treatment outcome can be predicted by multiple factors, including high seizure frequency.1,2 Perampanel (PER), a selective, noncompetitive AMPA receptor antagonist, is approved in >40 countries for adjunctive treatment of partial seizures, with or without secondarily generalized seizures, in patients with epilepsy aged ≥12yrs. This analysis evaluates the efficacy of PER in subjects with drug-resistant partial seizures based on their seizure frequency at the time of enrollment in the 3 Phase III double-blind (DB) studies.Methods: Subjects enrolled in the DB Phase III studies, receiving 1–3 concomitant AEDs, were randomized to placebo (PBO) or PER 2, 4, 8 or 12 mg. The DB treatment period consisted of a 6-week titration and 13-week maintenance period. Upon completion, subjects were eligible to enroll in the open-label extension (OLE) study. Subjects began the OLE study with a 16-week blinded conversion, in which subjects previously on PBO were switched to PER, while subjects receiving PER during the DB study continued to receive PER. Subjects then entered the OLE maintenance period. For this subanalysis, subjects were further grouped into those with baseline seizure frequency higher or lower than the median baseline seizure frequency for the overall population, which was 11.2.Results: Of the 1480 subjects randomized in the DB studies, 1217 were included in the OLE study; 609 subjects had baseline seizure frequency ≤11.2 and 608 patients had baseline seizure frequency >11.2. For the pooled PER group (all doses), the median percent reduction during the DB treatment period in subjects with baseline seizure frequency ≤11.2 was higher (30.3%) than in those with baseline seizure frequency >11.2 (24.2%). For the PBO group, the median percent reduction was 12.7% for subjects with baseline seizure frequency ≤11.2 and 17.5% for those with baseline seizure frequency >11.2. During the OLE conversion period when all subjects were treated with PER, the subjects with baseline seizure frequency ≤11.2 had a higher median percent reduction and responder rate, regardless of prior DB treatment (Figure 1). During Weeks 1–156 of the OLE maintenance period, there was no pattern showing a difference between the subjects, and PER treatment showed a reduction in seizure frequency over time.Conclusions: The results of this subanalysis show that, regardless of baseline seizure frequency, long-term treatment with PER consistently reduced seizure frequency. Initial treatment with PER appeared to show better results for those with a lower seizure frequency than higher; however, with longer treatment there was no difference between the groups. 1French.Epilepsia.2007;48:3. 2Loscher.Epilepsia.2010;51:89. Support: Eisai Inc.