Abstracts

Rationale: A historical-controlled, multicenter, double-blind study (SP902;NCT00520741) demonstrated the efficacy and safety of conversion to lacosamide (LCM) monotherapy in adults with focal seizures. Post-hoc analysis indicated that 42.4% of patients who enrolled in the study and 61.3% of patients who completed the Monotherapy Phase experienced a ≥50% reduction in seizure frequency/28 days compared with Baseline. 9.2% of patients who enrolled in the study and 14.4% of patients who completed the Monotherapy Phase were seizure free during the LCM Monotherapy Phase (Wechsler et al, Epilepsia, In Press). These additional post-hoc analyses of SP902 data explored potential patterns in efficacy outcomes after conversion to LCM monotherapy based on baseline characteristics. Methods: Patients (16-70 years) on 1-2 AEDs experiencing ≥2 to ≤40 focal seizures/28 days during a prospective 8-week Baseline were randomized to LCM 400 or 300 mg/day (3:1). The second background AED was required to be ≤50% of the minimum recommended maintenance dose per the US product label. LCM was initiated at 200 mg/day and increased (100 mg/day in weekly increments) to the randomized dose during a 3-week Titration Phase, which was followed by a 6-week Withdrawal of background AED Phase and a 10-week LCM Monotherapy Phase. The analysis was performed on the safety set (SS; all patients who received ≥1 LCM dose) and on the subpopulation who completed the LCM Monotherapy Phase (Completer Set, [CS]). The 50% responder rates (percentage of patients experiencing ≥50% reduction in seizure frequency/28 days compared to Baseline) and seizure freedom rates were analyzed during the 10-week LCM Monotherapy Phase for the total SS and CS (LCM 400 + 300 mg/day). Patients who discontinued the study prior to the Monotherapy Phase were considered to not be responders or seizure free. Results: Baseline demographic and epilepsy characteristics were generally similar between the SS (N=425) and the CS (n=271; SS/CS: mean age 40.6/41.2 years; mean time since first diagnosis 17.2/15.8 years; 45.9%/43.5% discontinued ≥3 AEDs prior to study entry (AED history); baseline median focal seizure frequency/28 days 6.6/6.5; 1 background AED 73.4%/73.1%). No difference was observed between patients on 1 versus 2 background AEDs (SS and CS). Numerically higher responder and seizure freedom rates were observed in patients with shorter epilepsy duration (Figure 1). The seizure freedom rates tended to be numerically higher in patients who previously discontinued ≤1 AED before study entry, however this same pattern was not observed for the 50% responder rates (Figure 2). Conclusions: The results of this post-hoc analysis suggested that in adults with uncontrolled focal epilepsy conversion to LCM monotherapy resulted in a tendency towards better efficacy outcomes in patients with shorter epilepsy duration. There was not a clear pattern in seizure response based on number of previously discontinued AED(s). Funded by UCB Pharma