Objective:

Assess long-term safety/tolerability/efficacy of adjunctive brivaracetam in children with primary generalized seizures (PGS).

Background:

Safety/tolerability/efficacy of brivaracetam in children with epilepsy have been demonstrated for up to 9.5 years of exposure.

Design/Methods:

Subgroup analysis of phase 3, open-label, long-term trial (N01266/NCT01364597; patients aged <17 years at core trial entry; ≤5 mg/kg/day brivaracetam tablet/oral solution [≤200 mg/day]). Pre-specified seizure-related outcomes were assessed for patients aged <2/≥2 years at core trial entry using daily record-card data. Kaplan-Meier-estimated brivaracetam retention and change in Achenbach Child Behavior Checklist (CBCL) 1.5-5/6-18 scores were assessed post-hoc.

Results:

68 patients had PGS at baseline (50.0% male; mean age: 6.7 years; median modal brivaracetam dose 3.63 mg/kg/day). 14 (20.6%)/54 (79.4%) patients were aged <2/≥2 years. 28 (41.2%) patients completed the trial; most common reasons for discontinuation (≥10% of patients): adverse event (22.1%), lack of efficacy (17.6%), withdrawn consent (11.8%). Kaplan-Meier-estimated retention at 12/36/60 months: 61.8%/47.7%/43.3%; similar proportions of patients discontinued due to treatment-emergent adverse events (TEAEs) or lack of efficacy. 61 (89.7%) patients had TEAEs (drug-related 19 [27.9%]; serious 25 [36.8%]; discontinuations 15 [22.1%]). In patients aged <2/≥2 years, median percent reduction in 28-day-adjusted total seizure frequency from baseline to end of evaluation period was 66.7%/56.9% (n=12/n=36); 50.0%/60.6% had ≥50% response in all seizures (n=12/n=33). 2/54 (3.7%) patients aged ≥2 years were seizure-free (entire evaluation period). Mean changes from baseline to last evaluation in Achenbach CBCL 1.5-5 raw syndrome scores (n=18) fluctuated around 0 and were of minimal/small amplitude, suggesting stability. Mean changes from baseline in Achenbach CBCL 6-18 raw syndrome scores (n=20) showed small numerical improvements for most syndromes. At last evaluation, most patients remained in baseline T-score categories (range: 61.1%-100%).

Conclusions:

Long-term adjunctive brivaracetam was well-tolerated and efficacious in children with PGS at baseline. Behavior/emotional function were generally stable (CBCL 1.5-5) or slightly improved (CBCL 6-18) during brivaracetam treatment.