title: Lacosamide use in children with epilepsy: Retention rate and effect of concomitant sodium channel blockers in a large cohort.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Departments of Neurology and Pediatrics, Perelman School of Medicine at the University of Pennsylvania, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, U.S.A.
authors.forename: Emily
authors.initials: E
authors.lastname: McGinnis
authors.affiliation: Departments of Neurology and Pediatrics, Perelman School of Medicine at the University of Pennsylvania, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, U.S.A.
authors.forename: Sudha Kilaru
authors.initials: SK
authors.lastname: Kessler
mesh_terms: D000081:Acetamides / Q000627:therapeutic use*; D000293:Adolescent; D000367:Age Factors; D017668:Age of Onset; D000927:Anticonvulsants / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D000078334:Lacosamide; D008297:Male; D026941:Sodium Channel Blockers / Q000627:therapeutic use*; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D000081:Acetamides; D000927:Anticonvulsants; D026941:Sodium Channel Blockers; D000078334:Lacosamide
keywords: Antiepileptic drug; Effectiveness; Mechanisms of action; Pediatric epilepsy; Refractory epilepsy