Abstracts

Rationale: In a phase III, randomized, double-blind trial (Study 304), subjects with refractory partial-onset seizures who were treated with once-daily eslicarbazepine acetate (ESL) 800 mg or 1200 mg as adjunctive therapy had significantly greater seizure frequency reduction than placebo-treated subjects. The Seizure Severity Questionnaire (SSQ), a multi-dimensional patient-reported assessment designed for use in clinical research, was used to determine whether the treatment groups also differed in their experience of seizure severity and bothersomeness. Methods: The SSQ total score (TS) and domain scores of frequency and helpfulness of warning signs before seizures (BS), severity and bothersomeness of ictal movement and altered consciousness during seizures (DS), cognitive, emotional, and physical aspects of postictal recovery after seizures (AS), and overall severity and bother (SB) were calculated at baseline and at the end of maintenance therapy (12‑week duration) from the per‑protocol population (N=547). ANCOVA models, adjusted for baseline scores, estimated least square mean (LSM) differences between placebo and ESL (two ESL arms combined) of the per‑protocol population. Subjects with no seizures at follow‑up were assigned minimum scores for each section. There were 56 subjects with seizures who responded no to both types of seizure manifestations (with movements/actions and altered consciousness only). These subjects were included in the analysis and assigned the minimum DS score. A sensitivity analysis was conducted excluding these subjects. Results: A baseline SSQ was completed by 544 subjects who had a mean duration of epilepsy of 20.9 (SD: 13.3) years. Their average age was 38.4 (SD: 12.2) years, 63.6% were Caucasian, and 51.1% were female. Overall, 441 subjects (81.1%) had a valid TS both at baseline and at the end of maintenance therapy. The LSM for TS among ESL subjects was significantly lower at the end of therapy compared to placebo subjects (p=0.006). LSMs also were significantly lower for DS (p=0.031) and SB (p=0.001). BS and AS LSMs were lower for ESL subjects but did not reach statistical significance. LSMs and differences are presented in Table 1. Sensitivity analysis results of TS and DS were similar and remained statistically significant. Conclusions: In this subanalysis of a phase III trial, ESL subjects had statistically-significantly better SSQ total scores, less severity and bother during seizures, and lower overall levels of seizure severity and bother than placebo subjects.