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.