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

摘要

Abstract 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 subscales. 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. Highlights ? Clinically meaningful improvements in health-related quality of life were observed with a ≥ 50% seizure frequency reduction. ? Further improvement in health-related quality of life was observed with greater reductions in seizure frequency. ? The efficacy of adjunctive eslicarbazepine acetate was associated with a positive impact on health-related quality of life.