Affiliation:
1. Department of Development and Regeneration, Pediatric Neurology Section University Hospitals Katholieke Universiteit Leuven Leuven Belgium
2. Department of Neuropediatrics and Muscle Disorders, Medical Center University of Freiburg Freiburg Germany
3. Department of Neuropediatrics Bethesda Children's Hospital Budapest Hungary
4. UCB Pharma Monheim am Rhein Germany
5. UCB Pharma Morrisville North Carolina USA
6. Department of Neurology Icahn School of Medicine at Mount Sinai Hospital New York New York USA
Abstract
AbstractObjectiveThis study was undertaken to evaluate the long‐term safety, tolerability, and efficacy of adjunctive brivaracetam (BRV) treatment in pediatric patients with epilepsy.MethodsA 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).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 and efficacious in reducing seizure frequency, and had high retention rates, with generally stable cognitive/behavioral scores in pediatric patients with epilepsy.
Subject
Neurology (clinical),Neurology
Reference36 articles.
1. Incidence, prevalence and aetiology of seizures and epilepsy in children
2. EMA.Briviact EPAR [product information].2022[cited 2022 Dec 8].https://www.ema.europa.eu/en/documents/product‐information/briviact‐epar‐product‐information_en.pdf
3. Food and Drug Administration.FDA. BRIVIACT® (brivaracetam) [full prescribing information].2021[cited 2022 Dec 7].https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/205836s009 205837s007 205838s006lbl.pdf
4. Safety and Tolerability of Adjunctive Brivaracetam in Pediatric Patients < 16 Years with Epilepsy: An Open-Label Trial
5. Pharmacokinetics, safety, and tolerability of intravenous brivaracetam in neonates with seizures: interim analysis of a phase 2/3, open‐label trial [abstract 99];Krauwinkel W;Epilepsia,2021