Abstracts

Rationale: Improved response in the treatment of partial seizures has been reported in several double-blind randomized trials in which pregabalin was used adjunctively with levetiracetam. This study assessed the impact of both number and class of concomitant AEDs used in addition to pregabalin and levetiracetam on efficacy and safety. Methods: Two similarly-designed, randomized, double-blind, placebo-controlled trials of adjunctive pregabalin therapy in patients with intractable partial-onset epilepsy were pooled. Only those patients taking levetiracetam during the baseline were selected for safety and efficacy analyses. Pregabalin dosages ranged from 150 to 600 mg/d, and were administered in both fixed- and flexible-dosage regimens. Male and female patients, 18 years or older, with a diagnosis of partial onset epilepsy comprised the study population. Efficacy variables including percent change from baseline in 28-day seizure rate, 50% and 75% responder rate, and seizure freedom were assessed in terms of whether patients had been receiving one, two, or three or more AEDs in addition to levetiracetam and pregabalin/placebo. Treatment-emergent adverse events were assessed using the same criteria. Results: Of 139 patients receiving, and refractory to, levetiracetam at the time of entering these studies, 53 were receiving one, 55 were receiving two, and 31 were receiving three or more additional AEDs. Of 90 ITT patients who received pregabalin (300mg/d, 600mg/d, or flexible-dosage), and levetiracetam in these studies, the most common additional AEDs were carbamazepine (67.9%), lamotrigine (45.1%) and topiramate (40.1%). Median baseline seizure rate was 9.4. Across all three groups, the Hodges-Lehman estimate for the pregabalin vs. placebo difference in percent change from baseline in seizure frequency was -24.5%, favoring pregabalin (95% CI: -40.7 to -8.5). The proportion of pregabalin 50% responders was 34.3%, 48.7% and 25.0% respectively, for patients receiving one, two or three additional AEDs. Similarly, pregabalin 75% responders constituted 11.4%, 17.9% and 12.5% respectively, of the same three groups. Overall, total 50% responders (37.4%) and 75% responders (13.2%) were significantly higher when compared with patients receiving placebo (14.9%; P=.0053; and 0.0% respectively). The most common TEAEs with pregabalin (≥5) were dizziness, blurred vision, vertigo, fatigue and weight gain in the first two groups. Apart from vertigo and fatigue, TEAE incidence decreased in patients using three or more additional AEDs. Conclusions: Number and class of concomitant AEDs are a concern when additional AED therapy is planned. Pregabalin, administered adjunctively with levetiracetam, is safe and effective for treatment of refractory partial seizures. These data suggest that 50% and 75% response rates improve with pregabalin when fewer than 3 or more AEDs have been used concomitantly with levetiracetam.