Abstracts

Rationale: To evaluate the efficacy and safety of lacosamide (LCM) as initial monotherapy for elderly patients with newly-diagnosed focal epilepsy, a subgroup analysis of patients ≥65 years in a double-blind, non-inferiority trial vs carbamazepine controlled-release (CBZ-CR; NCT01243177) was conducted. Methods: Patients were randomized 1:1 to twice-daily LCM or CBZ-CR. Flexible dosing (LCM 200/400/600mg/day; CBZ-CR 400/800/1200mg/day) was based on response to, and tolerability of the drug, reflecting clinical practice. Assessment of ‘pure’ efficacy was provided by Kaplan–Meier (KM)-predicted proportion of patients with 6-month seizure-freedom, following stabilization at last evaluated dose (LED) in full analysis (FAS) and per protocol (PPS) sets. Patients who were seizure-free at 6 months entered a 6-month maintenance period. Post hoc analyses included KM-predicted 12-month seizure-freedom at LED and from date of first trial dose (FAS only). Results: In total, 62 LCM- and 57 CBZ-CR–treated elderly patients received trial medication (FAS), of whom 57 and 48 had no important protocol deviations (PPS). Patient characteristics were similar between groups; however, number of comorbidities and past 3-month seizure frequency were higher among those randomized to LCM (Table 1). Most patients remained on the first dose level (LCM 55 [88.7%]; CBZ-CR 42 [73.7%]). Overall, 45/62 (72.6%) patients on LCM and 34/57 (59.6%) on CBZ-CR completed 6 months on LED without a seizure (FAS). KM-predicted 6-month seizure-freedom at LED was 93.6% with LCM vs 92.3% with CBZ-CR in FAS (treatment difference [95%CI] 1.4% [-8.9%, 11.6%]) and 96.3% vs 96.4% (-0.1% [-8.4%, 8.2%]) in PPS. The 12-month seizure freedom rate at LED was 59.7% with LCM and 50.9% with CBZ-CR. KM-predicted 12-month seizure-freedom at LED was 82.8% and 79.8%, respectively (treatment difference 3.0% [-14.2%, 20.3%]). KM-predicted proportion of patients remaining seizure-free at 12 months from the first dose was 70.6% with LCM vs 49.7% with CBZ-CR (treatment difference 20.9% [3.2%, 38.7%]). More patients on LCM (38/62 [61.3%]) than on CBZ-CR (29/57 [50.9%]) completed the trial. Discontinuations due to treatment emergent adverse events (TEAEs) were less common with LCM vs CBZ-CR (21.0% vs 26.3%; Table 2). Incidences of drug-related and serious TEAEs were lower with LCM than CBZ-CR. Of the most frequently reported TEAEs, only falls had ≥5% higher incidence with LCM than with CBZ-CR (Table 2). Conclusions: LCM demonstrated similar efficacy to CBZ-CR in elderly patients as assessed by 6 and 12-month seizure-freedom rates. LCM appeared to be better tolerated than CBZ-CR, despite the higher prevalence of comorbidities among patients randomized to LCM. Based on these results, and its known, favorable pharmacokinetic profile and low potential for drug–drug interactions, LCM may be a suitable monotherapy option for elderly patients with newly-diagnosed epilepsy. Funding: UCB Pharma-sponsored.