Abstracts

Rationale: Lacosamide (LCM) is among the newest antiepileptic drugs (AEDs) approved as adjunctive therapy for treatment of partial-onset seizures. Unlike traditional sodium channel blocking (SCB) agents that produce fast sodium channel inactivation, LCM appears to have a unique mechanism of action involving selective enhancement of sodium channel slow inactivation. We evaluated the impact of planned dose reduction of concomitant AEDs on tolerability in patients receiving LCM.Methods: Data was collected at 3 time points: LCM initiation (Visit 1), 3-6 month post LCM initiation (Visit 2) and 12-24 months post LCM initiation (Visit 3). Subjects were categorized as having planned reduction of concomitant AEDs or not based on documentation by the epilepsy provider at Visits 1 and 2. AEDs were categorized as SCB or non-SCB (NSCB). Groups with and without planned reduction were compared on presence and number of treatment emergent adverse events (TEAE) using chi-square tests or logistic regression and on time to LCM discontinuation with time-to-event methods. A standardized variable of the amount of AED taken daily was determined using established methods based on the assumed average daily AED dose assigned by the World Health Organization.Results: 106 adults (mean age 41.4 13.4; 53 [50%] males) seen in the Cleveland Clinic Epilepsy Center were started on LCM between 6/9/2009 and 6/9/2011 and had complete data at the designated visit intervals. Upon LCM initiation, 90 (84.9%) subjects were on polytherapy and 16 (15.1%) were on monotherapy. At the time of LCM initiation, dose reduction of concomitant AEDs was planned in 59 (55.7%) subjects, while AEDs were either unchanged, increased, or increased and decreased in 47 (44.3%). Fewer subjects with planned dose reduction had TEAE (49.2% vs. 68.1%, p=0.05) and these subjects had a lower risk of TEAE occurrence (OR 0.36, p=0.019) after adjusting for standardized AED dose. Subjects with dose reduction also had a lower risk of LCM discontinuation (OR 0.43) and longer time to LCM discontinuation (hazard ratio 0.45 [0.22, 0.93], p=0.03), adjusting for standardized AED dose. Among all cases, those who ever had TEAE had significantly higher standardized dose at Visits 2 and 3 (p=0.03 and p=0.02, respectively). Time to discontinuation of LCM was significantly longer for subjects not on SCB agents only at baseline (p=0.04) who were also less likely to discontinue LCM compared to those taking SCB agents (p=0.006).Conclusions: Planned dose reduction of concomitant AED therapy during LCM initiation is associated with a reduced risk of TEAE and LCM discontinuation. Discontinuation of LCM within 24 months of initiation is less likely in subjects taking NSCB than SCB agents. This study extends prior observations by considering total AED burden in the assessment of tolerability and further supports the benefits of early, planned dose reduction of concomitant AEDs at the time of LCM initiation in appropriate cases. This study was supported by UCB Pharma, Inc.