Associations between seizure severity change and patient characteristics, changes in seizure frequency, and health-related quality of life in patients with focal seizures treated with adjunctive eslicarbazepine acetate: Post hoc analyses of clinical trial results

Abstract The relationships between seizure severity change and patient characteristics, changes in seizure frequency, and health-related quality of life (HRQoL) may be important for determining the overall impact of medication therapy on patients with epilepsy. The objectives of these post hoc analyses of the global Phase III 093-0304 trial ( NCT00988429 , Study 304) of adjunctive eslicarbazepine acetate (ESL) in patients with refractory focal (partial-onset) seizures (FS) were to evaluate associations between seizure severity change, measured by the Seizure Severity Questionnaire (SSQ), and 1) patient characteristics, 2) seizure frequency change, standardized as the seizure frequency (SSF) per 28-day period, and 3) change in HRQoL, evaluated by the Quality of Life in Epilepsy Inventory-31 (QOLIE-31) and the Montgomery–Asberg Depression Rating Scale (MADRS). The analyses were conducted on the per-protocol population (PPP) of patients who were randomized to a placebo arm (n = 188) or an ESL-active group that included treatment with adjunctive ESL 800 mg once daily (QD; n = 184) or adjunctive ESL 1200 mg QD (n = 175). General linear models (GLM) were used to measure the association between SSQ change and patient baseline characteristics or percentage change in the SSF from baseline. Associations between changes in the SSQ and changes in the QOLIE-31 and MADRS were examined using GLM with patient baseline characteristics as covariates. Subgroup analyses were performed for patients in the ESL-active group and those treated with ESL 800 mg or ESL 1200 mg. Minimal clinically important difference (MCIDs) thresholds were used to assess improvements in SSQ scores. The analyses included 547 per-protocol patients. Patients using 1 antiepileptic drug (AED) at baseline had greater improvements in the SSQ compared with those receiving 2 AEDs (P = 0.0606). Treatment with ESL 1200 mg was significantly associated with clinically meaningful improvements in the SSQ (P = 0.0005). The SSQ improvements were significantly associated with an SSF reduction of ≥ 75%, compared with no reduction (P  These findings demonstrated that in this clinical trial population, adding ESL to baseline AED therapy had utility for decreasing seizure severity and improving HRQoL. There were no significant associations between changes in seizure severity and changes in depressive symptoms in patients with FS.