Abstracts

Rationale: Lacosamide is a new antiepileptic drug (AED) approved for the adjunctive treatment of partial-onset seizures in adults. The efficacy of adjunctive lacosamide was studied in three Phase II/III clinical trials in patients receiving stable doses of 1-3 concomitant AEDs. Many patients in these trials had a history of prior surgical intervention for epilepsy. This analysis further evaluates those patients, with a particular focus on vagal nerve stimulation (VNS) and resective surgery. Methods: Patients reporting prior surgical intervention for epilepsy were placed into mutually exclusive groups, based on type of procedure. For patients reporting more than one intervention, classification was based on a hierarchical system, with the more complex and/or invasive intervention taking precedence (i.e., patients reporting both VNS and resection were placed into the resection group for analysis). Efficacy was evaluated using the following endpoints from the trials, measured from baseline to the maintenance period: 1) percent change in seizure frequency per 28 days; and 2) proportion of patients experiencing a ≥50% reduction in seizure frequency. Results: Overall, 1,294 randomized patients were analyzed: 359 placebo and 935 lacosamide (dose range 200-600 mg/day). Prior surgical intervention for epilepsy was reported in 32.9% (n=426) comprising (based on hierarchical classification): VNS (46.9%), resection (39.9%), callosotomy (2.8%), craniotomy (8.7%), deep brain stimulation (DBS, 0.9%), or other (0.7%). Forty-five of the 426 patients reported both prior VNS and an additional surgical intervention (resection, callosotomy or DBS); these patients were represented in the latter groups. Comparable efficacy results were observed between patients reporting prior surgical intervention for epilepsy and those reporting no prior surgery. The lacosamide 400 mg/day dose group represented the largest number of patients and is used for reporting purposes. The median percent reduction in seizure frequency was 41.2% in the VNS group and 32.3% in the resection group, The proportion of patients achieving a ≥50% reduction in seizure frequency was 41.4% in the VNS group and 34.4% in the resection group, compared to 40.3% in patients reporting no prior surgery. Efficacy results were similar for the lacosamide 200 and 600 mg/day dose groups. Conclusions: In three Phase II/III trials, adjunctive lacosamide was equally effective in patients with no history of epilepsy surgery and patients reporting prior VNS or resective surgery for epilepsy, who are presumably more refractory to treatment.