Efficacy and tolerability of lacosamide monotherapy in elderly patients with newly diagnosed epilepsy: subgroup analysis of a non-inferiority trial versus controlled-release carbamazepine (P5.232)

Objective: To evaluate efficacy and tolerability of lacosamide monotherapy in elderly patients (≥65 years) with newly-diagnosed epilepsy. Background: Primary results of the SP0993 trial (NCT01243177) demonstrated non-inferiority of lacosamide vs controlled-release-carbamazepine (carbamazepine-CR). Design/Methods: Patients randomized 1:1 to lacosamide/carbamazepine-CR. Flexible dosing (lacosamide:200/400/600mg/day; carbamazepine-CR:400/800/1200mg/day) was based on seizure-control. Primary outcome: 6-month seizure-freedom at last-evaluated-dose (LED). Patients completing 6 months seizure-free entered 6-month maintenance-period. Subgroup analyses were performed for elderly patients; 12-month seizure-freedom on LED, and from date of first dose were evaluated post hoc . Results: 119 elderly patients received trial medication (full analysis set [FAS]: lacosamide: 62; carbamazepine-CR: 57); 105 had no important protocol deviations (per-protocol set [PPS]: 57; 48). Patients randomized to lacosamide had higher number of comorbidities (median [Q1, Q3]: 5.0 [3.0, 7.0] vs 4.0 [2.0, 7.0]) and higher past 3-month seizure-frequency (3.0 [2.0, 6.0] vs 2.0 [1.0, 4.0]) than those on carbamazepine-CR. Most patients remained on first dose level (lacosamide: 55 [88.7%]; carbamazepine-CR: 42 [73.7%]). Overall, 45/62 (72.6%) lacosamide-treated and 34/57 (59.6%) carbamazepine-CR-treated patients completed 6-months without seizure. Kaplan-Meier-estimated 6-month seizure-freedom was similar with lacosamide vs carbamazepine-CR (FAS: 93.6%, 92.3%; treatment-difference [95%CI]: 1.4% [−8.9%, 11.6%]) (PPS: 96.3%, 96.4%; −0.1% [−8.4%, 8.2%]). In FAS, 37/62 (59.7%) lacosamide-treated vs 29/57 (50.9) carbamazepine-CR-treated patients completed 12-months without seizure; Kaplan-Meier-estimated 12-month seizure-freedom was 82.8% vs 79.8% on LED (treatment-difference: 3.0% [−14.2%, 20.3%]), and 70.6% vs 49.7% at 12-months from first dose (20.9% [3.2%, 38.7%]). Treatment-emergent adverse events (TEAEs) occurred in 51/62 (82.3%) LCM-treated and 48/57 (84.2%) CBZ-CR-treated patients (drug-related TEAEs: 35.5%; 52.6%)(serious TEAEs: 12.9%; 21.1%)(severe TEAEs: 11.3%; 15.8%). 38/62 (61.3%) lacosamide-treated and 29/57 (50.9%) carbamazepine-CR-treated patients completed trial; 13 (21.0%) vs 15 (26.3%) discontinued due to TEAEs. Conclusions: Lacosamide demonstrated similar efficacy to carbamazepine-CR (6-and 12-month seizure-freedom) in elderly patients, and appeared to be better tolerated than carbamazepine-CR. Study Supported by: UCB Pharma Disclosure: Dr. Rosenow has received personal compensation for activities with Sandoz, Hexal, EISAI GmbH, cerbomed, Bayer-Vital UCB Pharma, Desitin GmbH, Shire, and Novartis as a consultant or speaker. Dr. Toledo has received personal compensation for activities with UCB Pharma, BIAL, EISAI, Esteve, and Shire as a consultant. Dr. Toledo has received research support from EISAI and BIAL. Dr Baulac received personal compensation for activities with EISAI, UCB, SAGE as a consultant and speaker. Dr Baulac has received research support from EISAI and UCB pharma. Dr. Terada has personal compensation for activities with UCB Pharma, GlaxoSmithKline, and Otsuka Pharmaceutical as a speaker. Dr. Li has received personal compensation for activities with UCB Pharma as an employee. Dr. Broch has received personal compensation for activities with UCB Pharma as an employee. Dr. Borghs has received personal compensation for activities with UCB Pharma as an employee. Dr. De Backer has received personal compensation for activities with UCB Pharma as an employee. Dr. Werhahn has received personal compensation for activities with UCB Pharma. Dr. Werhahn holds stock and/or stock options in UCB Pharma.