Fulton F Velez1, T Christopher Bond2, Kathryn P Anastassopoulos3, Xuezhe Wang4, Rui Sousa5, David Blum6, Joyce A Cramer7. 1. Sunovion Pharmaceuticals Inc., 84 Waterford Drive, Marlborough, MA 01752, United States. Electronic address: Fulton.Velez@sunovion.com. 2. Covance Market Access Services Inc., 9801 Washingtonian Blvd., 9th Floor, Gaithersburg, MD 20878, United States. Electronic address: Christopher.Bond@covance.com. 3. Covance Market Access Services Inc., 9801 Washingtonian Blvd., 9th Floor, Gaithersburg, MD 20878, United States. Electronic address: Kathryn.Anastassopoulos@covance.com. 4. Covance Market Access Services Inc., 9801 Washingtonian Blvd., 9th Floor, Gaithersburg, MD 20878, United States. Electronic address: Xuezhe.Wang@Covance.com. 5. Bial, Department of Research and Development, À Av. da Siderurgia Nacional, 4745-457 S. Mamede do Coronado, Portugal. Electronic address: Rui.Sousa@bial.com. 6. Sunovion Pharmaceuticals Inc., 84 Waterford Drive, Marlborough, MA 01752, United States. Electronic address: David.Blum@sunovion.com. 7. Independent consultant, 2207 Bancroft St., Houston, TX 77027, United States. Electronic address: joyce.cramer@gmail.com.
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.
RCT Entities:
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.