Abstracts

Rationale: This study aimed to describe lacosamide (LCM) use and effectiveness in a large pediatric epilepsy population in the first years of its availability, using retention rate as the primary outcome measure. Retention rate is a pragmatic measure of effectiveness, a combination of efficacy and tolerability. We hypothesized that patients concurrently taking other AEDs acting on sodium channels are at higher risk of LCM failure. Methods: In this single center retrospective cohort study, electronic medical records of all patients seen at CHOP from 1/2010 to 1/2012 were searched for patients with at least one LCM prescription and at least one follow up visit. Data were gathered by systematic manual chart review, with follow up data through 1/2013. The primary outcome was LCM failure, defined as discontinuation of LCM or initiation of an additional antiepileptic therapy. The impact of concomitant use of other Na channel AEDs (oxcarbazepine, carbamazepine, lamotrigine, or phenytoin) on retention rate was evaluated using Cox regression. Kaplan-Meier curves were generated for time to LCM failure, for all patients, and by concurrent use of Na channel AEDs. Results: Ninety-seven patients (42 female) were included for analysis. Thirty-nine patients were excluded for loss ot follow up (9), prior LCM use (9), lack of starting LCM despite prescription (5), and inadequate data (16). Median age at seizure onset was 2 years (range <1-16). Median age at starting LCM was 15 years (range 2-21). Median follow up time was 12 months (range <1-34). Mode of seizure onset was generalized in 7 (7%), focal in 70 (72%), both focal and generalized in 19 (20%), and spasms in 1(1%). Mean number of prior AEDs was 5 (range 1-14). Mean number of concomitant AEDs was 2 (range 0-6). Mean maximum dose of LCM was 6.3 mg/kg/day (range 1.4-22). For all patients combined, the success rate (probability of remaining on LCM without additional therapy) was 41% at 1 year and 27% at 2 years. For subjects not taking other Na channel AEDs, the success rate was 52% at 1 year and 38% at 2 years. For subjects taking Na channel AEDs, the success rate was 31% at 1 year and 15% at 2 years. The hazard ratio for LCM success in patients without other Na channel AEDs was (1.8, 95% CI 1.1-3.0) Side effects were noted in 22 (43%) patients taking Na channel AEDs, and in 8 (17%) of those not taking Na channel AEDs (p=0.008). Conclusions: In a large cohort of pediatric epilepsy patients, the perceived benefit-to-side effect balance for LCM is favorable enough that 40% will continue taking the medication for at least a year without need for additional therapy. Concurrent use of Na channel AEDs may be a risk factor for LCM failure, perhaps driven by the higher rate of side effects in this group.