Lacosamide use in children with epilepsy: Retention rate and effect of concomitant sodium channel blockers in a large cohort

Abstract

SUMMARYObjectives: To evaluate the effectiveness of lacosamide (LCM) in pediatric patients, using time to treatment failure as the outcome measure, and to assess the impact of concomitant sodium channel blocker (SCB) use on LCM retention. Methods: This is a retrospective cohort study of patients <21 years old receiving LCM from 2010 to 2015. Kaplan-Meier survival curves were generated for time to LCM failure, defined as discontinuation of LCM or addition of another antiepileptic therapy. The impact of concomitant use of traditional SCB agents (phenytoin, carbamazepine, oxcarbazepine, and/or lamotrigine) and other factors including age, seizure types, fast drug titration, and prior antiepileptic drug history were evaluated using Cox regression. Results: The analysis cohort included 223 patients, of whom 116 were taking one or more SCBs, with median follow-up of 7.4 months (1-53 months). For all patients, the probability of remaining on LCM without addition of another therapy was 44.7% at 12 months and 25.6% at 24 months. Concomitant SCB use was an independent predictor of time to LCM failure (hazard ratio [HR] 1.91, 95% confidence interval [CI] 1.38-2.65, p < 0.001).Although treatment emergent adverse effects were reported more often in patients taking SCB (65% vs. 39%, p < 0.001), intolerability was rarely the sole reason cited for LCM discontinuation, and SCB use was strongly associated with LCM failure, even when controlling for presence of treatment emergent adverse effects (adjusted HR 1.99, 95% CI 1.36-2.90, p < 0.001). Significance: This study provides observational evidence for treatment persistence of LCM in children, in a large cohort with long-term follow-up, using time to treatment failure as the outcome measure. Concomitant SCB use was a key factor increasing risk of LCM failure, but not due to treatment-emergent adverse effects alone.

Lacosamide in the treatment of patients with epilepsy and intellectual disabilities: A long‐term study of 136 patients

“…Concomitant AEDs were designated as SCB according to McGinnis et al and included oxcarbazepine (OXC), carbamazepine (CBZ), phenytoin (PHT), and lamotrigine (LTG). Follow‐up examinations were conducted mostly in our outpatient clinic, with the minimum follow‐up period being 4 weeks.…”

“…Adverse events are mostly dose dependent; restricted to the central nervous system and gastrointestinal system; and include dizziness, diplopia, somnolence, headache, nausea, and/or vomiting . Other trials have demonstrated a significant decrease in LCM efficacy in the presence of other SCBs …”

Long‐term efficacy of add‐on lacosamide treatment in children and adolescents with refractory epilepsies: A single‐center observational study

“…When considering the retention rate, only 8% of the 88 enrolled individuals maintained the initial treatment at 72 months. Two recent studies have assessed long‐term LCM efficacy in pediatric and mixed populations using the retention rate as outcome measure . Drug‐retention rate takes point out the period intervening between initiation and withdrawal of a medication, or its substitution with an alternative treatment and is considered an efficacy and tolerability index.…”

Untitled

“…Concomitant use of another sodium-channel blocking AEDs increased the likelihood of treatment failure [28]. Dosage: A starting dose of 1 mg/kg/day may be considered for initiation of therapy.…”