Severity and burden of partial-onset seizures in a phase III trial of eslicarbazepine acetate

•The SSQ is a multi-dimensional, patient-reported assessment used in clinical research to assess seizure severity and bother, comparing followup to baseline.•Eslicarbazepine acetate (ESL) led to statistically significant, dose-dependent reductions in seizure severity.•The reduction in seizure severity for the higher dose of ESL was clinically meaningful.•These findings complement published assessments of reductions in seizure frequency versus placebo treatment.

ObjectiveThe objective of this study was to compare posttreatment seizure severity in a phase III clinical trial of eslicarbazepine acetate (ESL) as adjunctive treatment of refractory partial-onset seizures.MethodsThe Seizure Severity Questionnaire (SSQ) was administered at baseline and posttreatment. The SSQ total score (TS) and component scores (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 bothersomeness [SB]) were calculated for the per-protocol population. Analysis of covariance, adjusted for baseline scores, estimated differences in posttreatment least square means between treatment arms.ResultsOut of 547 per-protocol patients, 441 had valid SSQ TS both at baseline and posttreatment. Mean posttreatment TS for ESL 1200 mg/day was significantly lower than that for placebo (2.68 vs 3.20, p < 0.001), exceeding the minimal clinically important difference (MCID: 0.48). Mean DS, AS, and SB were also significantly lower with ESL 1200 mg/day; differences in AS and SB exceeded the MCIDs. The TS, DS, AS, and SB were lower for ESL 800 mg/day than for placebo; only SB was significant (p = 0.013). For both ESL arms combined versus placebo, mean scores differed significantly for TS (p = 0.006), DS (p = 0.031), and SB (p = 0.001).ConclusionsTherapeutic ESL doses led to clinically meaningful, dose-dependent reductions in seizure severity, as measured by SSQ scores.Classification of evidenceThis study presents Class I evidence that adjunctive ESL (800 and 1200 mg/day) led to clinically meaningful, dose-dependent seizure severity reductions, measured by the SSQ.