Abstracts

Rationale: Lacosamide is a newer antiepileptic drug approved to a maximum dose of 400 mg/day as adjunctive treatment for partial-onset seizures (POS) in adults. The safety and efficacy of adjunctive lacosamide has been assessed in double-blind, placebo-controlled trials (lacosamide dose range 200 to 600 mg/day) and in long-term open-label extension (OLE) trials (lacosamide dose range 100 to 800 mg/day). This subgroup analysis evaluated the long-term efficacy and tolerability of lacosamide within the approved dose range (≤400 mg/day). Methods: Data were pooled from three long-term OLE trials (SP615; SP756 [Husain et al, Epilepsia 2012]; SP774) in adults with POS who completed a Phase II or III trial of adjunctive lacosamide. During open-label (OL) treatment, dosage adjustments of lacosamide (100 to 800 mg/day) and/or concomitant AEDs were allowed to optimize tolerability and seizure control. Outcomes were evaluated from the OLE studies for patients exposed to ≤400 mg/day lacosamide during the lead-in and OLE trials. Results: Of 1,054 patients who initiated OL lacosamide treatment, 34.4% (n=363) had been exposed only to lacosamide doses ≤400 mg/day, with 33.3% (121/363) of those patients completing the OLE trial and 89.3% (108/121) of completers continuing to commercial lacosamide treatment. At Baseline (lead-in trial), 83.7% (n=304) of patients included in this subanalysis were taking 2 to 3 AEDs and 71.9% (n = 261) had tried ≥4 lifetime AEDs. Baseline (lead-in trials) median seizure frequency per 28 days was 9.0 (range 2.5 - 404.5). A total of 66.7% (n = 242) of patients discontinued prior to the end of the exposure period (up to 8 years), most commonly for lack of efficacy (24.0%), adverse event (16.8%), and consent withdrawal (17.6%). The proportion of patients exposed to ≤400 mg/day lacosamide for >1, >2, >3, >4 and >5 years was 64.2%, 50.1%, 41.0%, 34.2%, and 15.7%. As all patients had an opportunity to complete at least 3 years of OL treatment, the lower rates of exposure after 3 years is attributed to study closure as well as premature discontinuations. The most commonly (≥10%) reported treatment-emergent adverse events (TEAEs) were dizziness (21.5%), headache (14.0%), and nasopharyngitis (10.7%); most were mild to moderate in intensity. For 1-, 2-, 3-, 4- and 5-year completer cohorts, the median percent reduction from Baseline in POS frequency per 28 days was 59.4%, 64.1%, 67.9%, 69.3% and 71.0%; Figure 1 depicts seizure reduction by cohort over time. The ≥50% responder rates for the 1-, 2-, 3-, 4- and 5-year completer cohorts were 60.2%, 65.9%, 68.0%, 72.6% and 70.2%; the ≥75% responder rates were 36.8%, 42.3%, 42.7%, 44.4%, and 49.1% (Figure 2). Conclusions: Used in the approved dose range (up to 400mg/day), long term adjunctive lacosamide was generally well tolerated and associated with a reduction in seizure frequency and a maintenance of efficacy. Sponsored by UCB