Abstracts

Rationale: 28-day baseline seizure rates vary within and among studies of pregabalin as adjunctive therapy for patients with refractory partial seizures. In all these studies, efficacy evaluations adjusted for baseline seizure variability; however, stratification of patients by baseline seizure rate was not feasible due to the size of the studies. The objective of this post hoc analysis was to evaluate the response to adjunctive pregabalin treatment based on the 28-day baseline seizure rate by pooling data from 6 similarly designed placebo-controlled studies of pregabalin in patients with refractory partial-onset seizures. Methods: Data from 6 randomized, double-blind clinical studies of pregabalin in patients with refractory partial-onset epilepsy were pooled for this analysis. Patients received adjunctive treatment with 150, 300, or 600 mg/day pregabalin; flexible-dose pregabalin; or placebo in addition to ?1 concomitant antiepileptic drug. Patients were grouped according to their 28-day baseline seizure rate (?5, >5 ?10, >10 ?23, >23) and response to pregabalin was analyzed using 50% Responder rate and RRatio. Responder rate was analyzed using logistic regression and RRatio by analysis of covariance with treatment as main effects and gender, age, duration since diagnosis, and baseline seizure rate as covariates. Results: A total of 1775 patients (male, n=869 [48.9%]) who received placebo (n=566), 150 mg/day (n=185) 300 mg/day (n=242), 600 mg/day (n=532) or flexible-dose (n=250) pregabalin were pooled for this analysis. The mean (standard deviation) baseline seizure rate was 26.4 (144.8), 24.7 (38.8), 20.5 (34.4), 20.3 (34.5) and 44.5 (443.0) for placebo, 150 mg/d, 300 mg/d, 600 mg/d, and flexible-dose pregabalin, respectively. Significant improvements in Responder rates were observed across all baseline seizure rates for 600 mg/day (odds ratio [OR] range: 5.7-7.9; P<0.0001) and flexible-dose (OR range: 2.5-3.5; P<0.05) pregabalin versus placebo. Significant benefits were also observed for 600 mg/day and flexible-dose pregabalin for least squares mean (LSM) difference in RRatio (range, -15.4 to -33.9; P?0.014) across all baseline seizure cut-offs, except for nonsignificant improvements for a baseline seizure rate of >