Long-term tolerability and efficacy of adjunctive brivaracetam in pediatric patients with generalized-onset seizures: Subgroup analysis of an open-label, follow-up trial

To assess long-term safety, tolerability, and efficacy of adjunctive brivaracetam in children with generalized-onset seizures. Subgroup analysis of a Phase 3, open-label trial (N01266/NCT01364597; ≤5 mg/kg/day brivaracetam [maximum 200 mg/day]) in patients aged ≥ 1 month to < 17 years with generalized-onset seizures at core trial entry. Seizure-related outcomes were assessed for patients aged < 2/≥2 years using daily record-card data. Kaplan-Meier-estimated retention and change in Achenbach Child Behavior Checklist (CBCL) scores were assessed post hoc. Of 257 patients receiving brivaracetam, 68 had generalized-onset seizures (50.0 % male; mean age: 6.65 years; median modal brivaracetam dose 3.6 mg/kg/day). Twenty-eight (41.2 %) patients completed the trial; most common reasons for discontinuation (≥10 % patients) were adverse event (22.1 %), lack of efficacy (17.6 %), and withdrawn consent (11.8 %). Kaplan-Meier-estimated retention at 1, 3, and 5 years was 61.8 %, 47.7 %, and 43.3 %, respectively. Sixty-one (89.7 %) patients had treatment-emergent adverse events (serious 25 [36.8 %]). In patients aged < 2/≥2 years (n = 12/n = 33), median percent reduction in 28-day-adjusted total seizure frequency from baseline to end of evaluation was 66.7 %/56.9 %; 50.0 %/60.6 % had ≥ 50 % reduction in all seizures. Mean changes from baseline to last evaluation in Achenbach CBCL 1.5-5 raw syndrome scores (n = 18) were all around 0 (minimal/small amplitude). Mean changes in CBCL 6-18 raw syndrome scores (n = 20) showed small numerical improvements for most syndromes. At last evaluation, most patients (range: 61.1 %-100 %) remained in baseline T-score categories. Long-term adjunctive brivaracetam was well tolerated and efficacious in children with generalized-onset seizures. Behavior/emotional function were generally stable or slightly improved.