Abstracts

Rationale: Pooled data from Phase III trials of perampanel were analyzed to explore the relationship between quality of life and reductions in the frequency of refractory partial seizures. Methods: Three Phase III clinical trials evaluated the efficacy and safety of adjunctive perampanel in patients with uncontrolled partial seizures (studies 304 [NCT00699972]; 305 [NCT00699582]; 306 [NCT00700310]). Trials included a 6-week Baseline Period and a Double-Blind Treatment Phase (6-week Titration; 13-week Maintenance). Percent changes in seizure frequency between Baseline and the Double-Blind Phase were recorded. Patients were classed as responders if seizure frequency was reduced by ≥50% between Baseline and Maintenance. Quality of Life in Epilepsy (QOLIE)-31P (questionnaire with 30 items across seven subscales [seizure-worry, overall quality of life, emotional well-being, energy-fatigue, cognition, medication effects, and social function] and one item on overall health status) was administered at Baseline and End Of Treatment (EOT) in patients (≥18 years). The minimally important difference (MID) for QOLIE was defined as an 11.8% change in overall score (Wiebe et al. J Neurol Neurosurg Psychiatry 2002; 73: 116-120). Multivariate regressions were used to estimate (a) marginal changes in QOLIE associated with a 1% reduction in seizure frequency, and the reduction in seizure frequency required to produce QOLIE MID, and (b) marginal changes in QOLIE in responders; changes greater than the MID established a direct correlation between the responder definition and QOLIE MID. Results: Of 1478 patients in the pooled intent-to-treat analysis set, 959 perampanel-treated patients from studies 304 (n=183), 305 (n=262) and 306 (n=514) had QOLIE data; 742 had complete data for inclusion in the multivariate analysis. Mean (SD) QOLIE scores at Baseline were 57.4 (16.7), 55.0 (14.7) and 55.6 (15.8) for the three trials, respectively. Overall, 62.4% of patients had Baseline QOLIE scores <50 and mean improvement at EOT was 12.5% (p=0.01). A 48.0% reduction in seizure frequency was required to produce QOLIE MID and a 1% reduction in seizure frequency was associated with a change of 0.01 in overall QOLIE score (p=0.03). Compared with non-responders, responders (27.9% of perampanel patients) had greater mean improvements in overall QOLIE (additional 21.1% beyond that achieved in non-responders), and the subscales for seizure-worry (55.3%), cognition (35.1%), and emotional well-being (38.1%; p<0.01 for all); these mean improvements were greater than the MID. Conclusions: Refractory partial seizures have a major impact on well-being, with most patients in this analysis having overall QOLIE scores <50 at Baseline. A 48% reduction in the frequency of these seizures was associated with a significant, meaningful improvement in overall quality of life. In addition, responder rate, defined by a ≥50% reduction in seizure frequency, corresponded with significant improvements in quality of life according to the QOLIE MID. Support: Eisai Inc