Long-term efficacy and tolerability of brivaracetam in pediatric patients with focal-onset seizures and cognitive or learning comorbidities: Post hoc analysis of an open-label trial

Abstract

ObjectiveEfficacy, tolerability, and behavioral/executive functioning during long-term adjunctive brivaracetam treatment were assessed in pediatric patients with focal-onset seizures (FOS) with/without cognitive/learning comorbidities (CLC). MethodsPost hoc analysis of a phase 3 open-label follow-up trial (N01266/NCT01364597). Patients with FOS (<16 years at core trial entry; direct enrollers ≥4–<17 years) received ≤5mg/kg/day brivaracetam (≤200mg/day). Subgroup analyses were performed for patients with and without ongoing CLC at baseline. ResultsPatients with CLC (84/185 [45.4%]) had longer epilepsy duration and higher number of prior antiseizure medications. Kaplan-Meier–estimated brivaracetam retention at 1, 3, and 5 years was 75.0%/78.2%, 61.9%/61.9%, and 52.2%/53.3% in patients with/without CLC. Efficacy assessments (patients >2 years of age) showed numerically lower median percent reduction in FOS frequency/28 days (43.8%/74.1% [n = 63/60]), 50% responder rates for FOS (46.0%/61.7% [n = 63/60]), and ≥12-month continuous freedom from all seizures (31.7%/55.9% [n = 60/68 patients with ≥12 months treatment]) in patients with/without CLC. Treatment-emergent adverse events were reported in 94.0%/95.0% of patients with/without CLC (serious: 33.3%/27.7%; drug-related: 31.0%/33.7%). From baseline to last evaluation, most patients with/without CLC had no shift in T-score category for each Achenbach Child Behavior Checklist (CBCL) 1.5–5 syndrome (≥50.0%/≥72.2%), CBCL 6–18 syndrome (≥66.0%/≥69.1%), and Behavior Rating Inventory of Executive Function scale (≥66.7%/≥69.0%). ConclusionsThese data indicate that brivaracetam could be an efficacious and well-tolerated treatment option for pediatric patients with FOS with and without CLC. Behavior and executive functioning were generally stable or slightly improved in patients with and without CLC.