RESUMEN
OBJECTIVE: This study was undertaken to evaluate the long-term safety, tolerability, and efficacy of adjunctive brivaracetam (BRV) treatment in pediatric patients with epilepsy. METHODS: A phase 3, open-label, multicenter, long-term follow-up trial (N01266; NCT01364597) was conducted on patients (aged 1 month to <17 years at core trial entry; direct enrollers aged 4 to <17 years) treated with BRV. Outcomes included treatment-emergent adverse events (TEAEs), behavior assessments (Achenbach Child Behavior Checklist [CBCL], Behavior Rating Inventory of Executive Function [BRIEF]/BRIEF-Preschool version [BRIEF-P]), and efficacy outcomes (percent change in focal seizure frequency, 50% responder rate for all seizure types for patient subgroups <2 years and ≥2 years of age using daily record card data). RESULTS: Of 257 patients with ≥1 dose of BRV (141 [54.9%] male; mean age = 8.0 years [SD = 4.5]), 36 patients were <2 years of age, and 72.0% of patients had a history of focal seizures. Mean BRV exposure was 3.2 patient-years. At least one TEAE occurred in 93.4% patients, and 32.3% had serious TEAEs. Seven patients died during the trial; no deaths were considered treatment-related. Patients ≥2 years of age had a median decrease in 28-day adjusted focal seizure frequency of 62.9%, and 50.9% had a ≥50% response in all seizures. Patients <2 years of age had a median decrease in 28-day adjusted focal seizure frequency of 96.9%, and 68.2% had a ≥50% response in all seizures. Kaplan-Meier estimated treatment retention was 72.7%, 64.5%, 57.8%, 53.3%, 50.1%, and 44.8% at 1, 2, 3, 4, 5, and 6 years, respectively. Mean changes (baseline to last evaluation) for all Achenbach CBCL and BRIEF-P/BRIEF subscale scores were negative, reflecting stability/slight improvement. SIGNIFICANCE: Long-term adjunctive BRV treatment was generally well tolerated and efficacious in reducing seizure frequency, and had high retention rates, with generally stable cognitive/behavioral scores in pediatric patients with epilepsy.
