Lacosamide tolerability in adult patients with partial-onset seizures: Impact of planned reduction and mechanism of action of concomitant antiepileptic drugs

•We studied the impact of AED planned reduction and mechanism on LCM tolerability.•106 adults with partial epilepsy seen 3-6 and 12-24 months post-LCM treatment•Less adverse events (AEs)/LCM discontinuation with planned AED reduction•Higher risk of AEs/LCM discontinuation with traditional sodium channel blockers•Novel analyses adjusting for standardized dose, a measure of concomitant AED load

ObjectiveWe evaluated the impact of planned dose reduction and mechanism of action of concomitant AEDs on tolerability in adults with partial-onset seizures undergoing lacosamide (LCM) titration.MethodsData were collected at baseline and 3-6 and 12-24 months post-LCM initiation. Subjects were categorized as having planned reduction of concomitant AEDs or not; AEDs were categorized as traditional sodium channel blockers (TSCB) or non-TSCB (NTSCB). Groups with/without planned reduction were compared on the presence and number of treatment-emergent adverse events (TEAEs) using chi-square tests or logistic regression and on time to LCM discontinuation with time-to-event methods controlling for standardized (STD) AED dose, a measure of concomitant AED load. Similar analyses were performed comparing subjects taking TSCB and NTSCB agents and used to identify relationships with ≥ 50% decreases in seizure frequency.ResultsOne hundred six adults (mean age 41.4 ± 13.4; 50% male) underwent LCM titration from June 2009-2011 with complete data. Reduction of concomitant AEDs was planned at the time of LCM initiation in 59 (55.7%) subjects. Fewer subjects with planned reduction had TEAEs (49.2% vs. 68.1%; p = 0.05), and these subjects had a lower risk of TEAEs (OR 0.36; p = 0.019) after adjusting for STD AED dose. The hazard ratio (95% CI) for LCM discontinuation was 0.46 (0.23, 0.94) in subjects with planned reduction of concomitant AEDs vs. others (p = 0.033) and 3.29 (1.01, 10.70) in subjects taking TSCB vs. NTSCB agents (p = 0.048). Among all cases, those who ever had TEAEs had significantly higher STD dose at both follow-up visits (p = 0.033 and p = 0.023, respectively). Seizure outcomes were not significantly different between groups at the last follow-up assessment.SignificancePlanned reduction of concomitant AEDs during LCM initiation and the use of NTSCB agents only are associated with a reduced risk of TEAEs and LCM discontinuation in adults with partial-onset seizures. This study extends prior observations by considering total AED load in the assessment of tolerability and supports the benefits of early reduction of concomitant AEDs during LCM initiation.