Abstracts

Rationale: Lacosamide (LCM) is a newer antiepileptic drug (AED) approved (up to 400 mg/day) as adjunctive treatment for partial-onset seizures (POS) in adults. Data from three open-label extension (OLE) trials have shown that long-term adjunctive LCM has been generally well tolerated and associated with reduction in seizure frequency and maintenance of efficacy [Rosenfeld et al, Epilepsy Currents 2012;12(S1):217]. This post-hoc analysis evaluated the long-term effects of adjunctive LCM in controlling complex partial seizures (CPS) and partial seizures with secondary generalization (PSSG) in adults with focal epilepsy. Methods: Data pooled from three OLE trials (up to 8 years) of adjunctive LCM in adults with POS (NCT00552305; NCT00522275; NCT00515619), allowing dose adjustment of LCM (100 800 mg/day) and/or concomitant AEDs. Responder rates ( 50%) and freedom from PSSG and combined CPS and PSSG were assessed in patients reporting PSSG and CPS or PSSG, respectively, during the Baseline period of the primary double-blind, placebo-controlled trial. The 50% responder rates were assessed based on yearly completer cohorts. The percentage of patients free from PSSG and combined PSSG and CPS for 3, 6 and 12 months were calculated for i) patients with 3, 6 and 12 months exposure, respectively, and ii) based on yearly completer cohorts.Results: Of the 1054 patients treated with adjunctive LCM during the OLE trials (mean epilepsy duration 24 years; 46% tried 7 lifetime AEDs; 84% on 2 3 concomitant AEDs), 435 reported PSSG (median 3.1 seizures/28 days) and 1001 reported CPS or PSSG (median 9.0 seizures/28 days) at baseline (primary trial). During OL LCM treatment, the overall 50% responder rate for PSSG was 58.5% (1-year), 66.1% (3-year), and 69.0% (5-year). The overall 50% responder rate for combined CPS and PSSG was 54.2% (1-year), 61.3% (3-year), and 66.9% (5-year) (Figure 1). The percentage of 50% responders within each completer cohort was sustained over time for PSSG and combined CPS and PSSG. Overall, 64.5%, 48.1% and 35.6% of patients exposed to LCM for 3, 6 and 12 months were free from PSSG for 3, 6 and 12 months, respectively, at any time during the OLE. The corresponding values for freedom from combined CPS and PSSG were 35.9%, 23.0% and 15.7% (Figure 2). In the yearly completer cohorts between 35.7% (1-year), 41.7% (3-year), and 46.4% (5-year) of patients experienced 12 months of freedom from PSSG, and between 15.7% (1-year), 20.3% (3-year), and 29.3% (5-year) of patients experienced 12 months of freedom from combined CPS and PSSG.Conclusions: Long-term adjunctive LCM treatment resulted in a clinically relevant response in CPS and PSSG in adults with long-lasting and difficult-to-treat focal epilepsy. Despite the potential bias induced by using data from open-label, flexible-dose studies to evaluate efficacy, these results provide additional information on the long-term effects of adjunctive LCM in settings closely reflecting clinical practice. UCB Pharma-Funded