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 number :
2.254
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Year :
2023
Submission ID :
393
Source :
www.aesnet.org
Presentation date :
12/3/2023 12:00:00 AM
Published date :
Authors :
Presenting Author: Lieven Lagae, MD, PhD – Pediatric Neurology, University Hospitals KU Leuven, Leuven, Belgium
Dimitrios Bourikas, PhD – UCB Pharma, Alimos, Greece; Najla Dickson, MD – UCB Pharma, Morrisville, NC, USA; Svetlana Dimova, MD, PhD – UCB Pharma, Brussels, Belgium; Sami Elmoufti, MSc – UCB Pharma, Morrisville, NC, USA; Brian Moseley, MD – UCB Pharma, Morrisville, NC, USA; Harriet Kang, MD – Department of Neurology, Icahn School of Medicine at Mount Sinai Hospital, New York, NY, USA
Rationale:
Cognitive comorbidities are common in children with epilepsy. This post hoc analysis evaluated the long-term tolerability and efficacy of adjunctive brivaracetam (BRV) in pediatric patients with focal-onset seizures with or without cognitive or learning comorbidities (CLC).
Methods:
Post hoc analysis of a phase 3, open-label, follow-up trial (N01266; NCT01364597). Patients with focal-onset seizures ( ≥1 month to <17 years of age at core trial entry) received ≤5mg/kg/day BRV (tablet/oral solution; max dose ≤200 mg/day). Subgroup analyses were performed for patients with and without ongoing CLC at baseline.
Results:
Of 185 patients with focal-onset seizures, 84 (45.4%) had ongoing CLC at baseline; most commonly developmental delay (14.6%), attention deficit/hyperactivity disorder (10.8%), and mental retardation (intellectual disability; 7.0%). Patients with versus without CLC were more commonly male, had a longer mean epilepsy duration, reported a higher incidence of prior/ongoing comorbid conditions (most commonly neurological or psychiatric), and a higher proportion had used ≥5 prior ASMs (Table). The median BRV treatment duration was 35.4 months in both subgroups. Overall, 52.4% of patients with and 49.5% without CLC completed the study. The estimated BRV treatment retention (Kaplan-Meier analysis) at 1, 3, and 5 years was 75.0%, 61.9% and 52.2% in patients with CLC, and 78.2%, 61.9% and 53.3% in those without CLC. Generally, no differences were observed between patients with and without CLC in the estimated proportion of BRV discontinuations due to lack of efficacy or due to TEAEs (Figure). Efficacy assessments (patients >2 years of age) showed numerically lower median percent reduction in 28 day focal seizure frequency (43.8/74.1% [n=63/60]), 50% responder rates for focal-onset seizures (46.0/61.7% [n=63/60]), and ≥12 month continuous seizure freedom (all seizure types; patients with ≥12 months treatment) (31.7/55.9% [n=60/68]) in patients with versus without CLC. TEAEs were reported in 94% and 95% of patients with vs without CLC, respectively (serious TEAEs: 33.3/27.7%; severe TEAEs: 19.0/12.9%; drug-related TEAEs: 31.0/33.7%; discontinuations due to TEAEs: 7.1/9.9%).
Conclusions:
In this analysis, pediatric patients with focal-onset seizures and ongoing CLC (45.4%) were generally more difficult to treat than those without CLC. Although the observed efficacy response was numerically lower in patients with versus without CLC, it still indicated a clinically relevant seizure frequency reduction. These data indicate that BRV could be an efficacious and well tolerated treatment option for pediatric patients with and without CLC.
Funding:
UCB Pharma-sponsored
Anti-seizure Medications