Abstracts

Rationale: Antiepileptic drugs (AEDs) are used to treat patients with focal seizures (FS). Prior studies have shown that treatment with AEDs, such as eslicarbazepine acetate (ESL), might be associated with a reduction in seizure severity. However, the relationships between seizure severity, health-related quality of life (HRQoL,) and depression are not well documented. A post hoc analysis from a Phase 3 global clinical trial (ClinicalTrials.gov NCT00988429) of adjunctive ESL vs. placebo was conducted to examine the associations of seizure severity with HRQoL and symptoms of depression. Methods: 653 patients with FS were randomized to placebo, ESL 800 mg QD, or ESL 1200 mg QD. Seizure severity was measured with the Seizure Severity Questionnaire (SSQ), HRQoL with the Quality of Life in Epilepsy Inventory-31 (QOLIE-31), and symptoms of depression with the Montgomery-Åsberg Depression Rating Scale (MADRS). Change scores were calculated as the difference between the end of the maintenance period (week 14) and baseline. Linear regression models examined associations between change in SSQ total score (TS) and change in 1) QOLIE-31 and 2) MADRS, controlling for baseline patient characteristics and baseline QOLIE-31 and baseline MADRS, respectively. Subgroup analyses were conducted among patients treated with ESL, ESL 800 mg, and 1200 mg. Results: The analysis included 547 per-protocol patients, of whom 51% were female and median age was 38 years. A 1-point reduction in SSQ TS at week 14 was significantly associated with a 2.39-point improvement in QOLIE-31 TS (95% confidence interval [CI]: 1.57, 3.20; P<0.0001). All QOLIE-31 subscales (especially seizure worry, social functioning, and overall QoL), showed significant improvement with a 1-point reduction in SSQ TS except Medication Effects (Table). Improvement results were similar for QOLIE-31 TS among the ESL-treated subgroup (n=359; 2.43 [95% CI: 1.41, 3.45]; P<0.0001) and subscale scores. The improvement was greater in the ESL 1200 mg subgroup (n=175; 3.32 [95% CI:1.87, 4.77]; P<0.0001) compared with the ESL 800 mg subgroup (n=184; 1.59 [95% CI: 0.10, 3.08]; P=0.0362) (Table). Similarly, among all patients (ESL+placebo; n=547), a 1-point reduction in SSQ TS at week 14 was significantly associated with a 0.39-point improvement in MADRS TS (95% CI: 0.05, 0.74; P=0.025). A similar association was observed among the subgroup of ESL-treated patients; however, it was not significant (P=0.0598). Conclusions: This post hoc analysis of a Phase 3 clinical trial suggests that improvements in seizure severity were associated with improvements in HRQoL as measured by QOLIE-31. Particularly, significant improvements were observed in seizure worry and social functioning domains. There was a trend for improvement in seizure severity associated with improvement and no worsening in depression symptoms. However, further analyses with a large sample size are warranted. Funding: Study funding provided by Sunovion Pharmaceuticals Inc.