Impact of seizure frequency reduction on health-related quality of life among clinical trial subjects with refractory partial-onset seizures: A pooled analysis of phase III clinical trials of eslicarbazepine acetate

Background: Subjects who received eslicarbazepine acetate (ESL) as adjunctive therapy experienced significantly greater seizure frequency reduction (SFR) than placebo in three phase III, randomized, double-blind trials. This analysis compared changes in health-related quality of life (HRQOL) between treatment responders and non-responders across the pooled, per-protocol population (N = 842) using the validated Quality of Life in Epilepsy Inventory -31 (QOLIE-31). Methods: QOLIE-31 scores were calculated for Total Score (TS) and seven subscales; higher scores indicate better HRQOL. Mean changes from baseline were calculated. Analysis of covariance examined least square mean (LSM) differences in final scores between responders (>= 50% and >= 75% SFR) and non-responders. Clinical significance was based on established minimal clinically important differences (MCIDs). Results: Mean changes were greater among responders for TS (5.2 versus 1.4 for >= 50% SFR; 7.5 versus 1.9 for >= 75% SFR) and all subscales. Additionally, the percentage of subjects with changes meeting or exceeding MCIDs was higher among responders for TS (48.4% versus 33.9% for >= 50% SFR; 56.9% versus 35.8% for >= 75% SFR) and all sub scales. Responders had significantly higher final scores for TS (LSM difference = 4.0 for >= 50% SFR; LSM difference = 5.7 for >= 75% SFR) and all subscales except emotional well-being at >= 50% SFR. LSM differences exceeded MCIDs at >= 75% SFR for TS and five of seven subscales, and two subscales at >= 50% SFR. In a subgroup analysis with placebo removed, LSM differences were larger overall. Significance: In clinical trials of adjunctive ESL, higher levels of SFR were associated with greater improvements in HRQOL. (C) 2016 Elsevier Inc. All rights reserved.