Cognitive and Behavioral Effects of Adjunctive Brivaracetam in Children and Adolescents with Focal Seizures: Final Data From an Open-label Follow-up Trial (P14-1.007)

Abstract

<h3>Objective:</h3> Evaluate cognitive and behavioral effects of long-term adjunctive brivaracetam (BRV) in children with focal seizures. <h3>Background:</h3> Children with epilepsy are at increased risk for cognitive and behavioral problems. <h3>Design/Methods:</h3> Post-hoc analysis of phase 3, open-label, follow-up trial (N01266; NCT01364597; patients &lt;16 years at core trial entry; ≤5 mg/kg/day BRV tablet/oral solution [≤200 mg/day]). Planned trial duration ≥3 years. Outcomes included Achenbach Child Behavior Checklist (CBCL; ages 1.5–5 and 6–18 years), Behavior Rating Inventory of Executive Function (BRIEF; ages 2–&lt;5 [BRIEF-P] and 5–16 years). <h3>Results:</h3> 140 patients were included (mean age 9.5 years; 22.9% aged 1.5–5 years [median exposure 3.6 years], 77.1% aged 6–16 years [median exposure 3.5 years]). Mean changes (baseline to last evaluation) for all Achenbach CBCL and BRIEF-P/BRIEF subscale scores were negative, reflecting stability/slight improvement. The largest decreases in CBCL were for aggressive behavior and anxious/depressed (both age groups) and other problems (1.5–5 years). The largest decreases in BRIEF-P/BRIEF scores were for inhibit and working memory (both age groups) and emotional control (2–&lt;5 years). Most patients had no shift in T-score category (baseline to last evaluation) for each CBCL subscale (between normal and borderline clinical range [BCR]) and BRIEF-P/BRIEF subscale (between normal and potential clinical significance [PCS]). For all CBCL subscales, higher proportion of patients changed from BCR to normal than from normal to BCR. Changes for BRIEF-P were mostly PCS to normal; for BRIEF, similar proportions of patients changed in either direction. Treatment-emergent adverse events (TEAEs) were reported in 100% and 95.4% of patients aged 1.5–5 and 6–16 years (drug-related TEAEs 31.3%, 30.6%; discontinuations due to TEAEs 6.3%, 9.3%). <h3>Conclusions:</h3> Cognitive and behavioral functioning scores in children and adolescents with focal seizures during long-term adjunctive BRV therapy were generally stable or slightly improved. BRV was generally well tolerated. <b>Disclosure:</b> Dr. Elshoff has nothing to disclose. Ms. Fleyshman has nothing to disclose. The institution of Mrs. De la Loge has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for IPSEN. The institution of Mrs. De la Loge has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for UCB. Dr. Dickson has received personal compensation for serving as an employee of UCB. Dr. Reichel has received personal compensation for serving as an employee of UCB Pharma. Dr. Reichel has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for UCB Biosciences. Dr. Reichel has received stock or an ownership interest from UCB Pharma. Dr. Floricel has received personal compensation for serving as an employee of UCB Biosciences GmbH. Dr. Floricel has received stock or an ownership interest from UCB Biosciences GmbH. Dr. SMEYERS has nothing to disclose.