Long‐term safety and efficacy of adjunctive brivaracetam in pediatric patients with epilepsy: An open‐label, follow‐up trial

Abstract

ObjectiveTo evaluate the long‐term safety, tolerability, and efficacy of adjunctive brivaracetam (BRV) treatment in pediatric patients with epilepsy.MethodsPhase 3, open‐label, multicenter, long‐term follow‐up trial (N01266; NCT01364597; 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‐P/BRIEF]), 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).ResultsOf 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.SignificanceLong‐term adjunctive BRV treatment was generally well tolerated, efficacious in reducing seizure frequency, and had high retention rates, with generally stable cognitive/behavioral scores in pediatric patients with epilepsy.

New Pharmacological Therapies in the Treatment of Epilepsy in the Pediatric Population

“…However, in patients after the age of 2 years, 60.3%, 63%, and 50.9% were similarly affected. The study proved that long-term use of BRV in children, although often associated with adverse symptoms, significantly reduced the incidence of focal or generalized seizures [ 79 ].…”

“…Although a sizable group of patients experienced side effects, they were relatively mild. BRV is a new drug that doctors will increasingly use in children affected by various types of epilepsy [ 73 , 75 , 78 , 79 , 80 , 81 ]. Table 5 summarizes the studies documenting the effectiveness of brivaracetam.…”

Narrative Review of Brivaracetam: Preclinical Profile and Clinical Benefits in the Treatment of Patients with Epilepsy

“…In a phase II, open-label trial (NCT00422422), BRV oral solution (0.8–4.0 mg/kg/day) was generally well tolerated and exhibited linear PK in pediatric patients (1 month to < 16 years of age) with epilepsy [ 61 ]. In a phase III, open-label extension trial (NCT01364597), the long-term safety, tolerability, and efficacy of adjunctive BRV was established up to 9.5 years in pediatric patients (aged 1 month to < 17 years of age) with epilepsy [ 62 ]. TEAEs occurred in 93.4% of patients and were considered drug related by the investigator in 30.7% of patients.…”

“…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. Behavior and cognitive functioning scores were generally stable or slightly improved with BRV [ 62 ].…”