Cognitive and Behavioral Effects of Adjunctive Brivaracetam in Children and Adolescents with Focal Seizures: Final Data from an Open-label Follow-up Trial
Abstract number :
3.284
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Year :
2022
Submission ID :
2203956
Source :
www.aesnet.org
Presentation date :
12/5/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:22 AM
Authors :
Jan-Peer Elshoff, PharmD, PhD – UCB Pharma; Sofia Fleyshman, BSc, MSc – UCB Pharma; Christine De la Loge, MSc – PCOM Analytics; Najla Dickson, MD – UCB Pharma; Christoph Reichel, PhD – UCB Pharma; Florin Floricel, MD, PhD – UCB Pharma; Patricia Smeyers, MD, PhD – Hospital Universitario y Politecnico La Fe de Valencia
Rationale: To evaluate cognitive and behavioral effects of long-term adjunctive brivaracetam (BRV) in children and adolescents with focal seizures.
Methods: Post hoc analysis of final data from a phase 3, open-label, follow-up trial (N01266; NCT01364597; patients < 16 years of age at entry into core trial; max 5 mg/kg/day BRV tablet or oral solution, not to exceed 200 mg/day). Planned trial duration was ≥3 years. Cognitive and behavioral outcomes were assessed with Achenbach CBCL (patients aged 1.5–5 and 6–16 years) and BRIEF-P/BRIEF (patients aged 2– < 5 and 5–16 years).
Results: A total of 140 patients were analyzed (mean age 9.5 years; 80 [57.1%] male; 32 [22.9%] aged 1.5–5 years [median exposure 3.6 years], 108 [77.1%] aged 6–16 years [median exposure 3.5 years]). Mean changes from baseline to last evaluation in raw subscale scores were (i) Achenbach CBCL 1.5–5 aggressive behavior −1.4, anxious/depressed −1.5, attention problems −0.5, emotionally reactive −1.0, sleep problems −1.1, somatic complaints −0.9, withdrawn −0.7, other problems −3.2 (N=32); (ii) Achenbach CBCL 6–18 aggressive behavior −1.9, anxious/depressed −1.5, attention problems −1.4, rule-breaking behavior −0.6, social problems −0.9, somatic complaints −1.0, thought problems −0.7, withdrawn/depressed −0.0 (N=102); (iii) BRIEF-P inhibit −6.6, shift −2.1, emotional control −4.9, working memory −4.0, plan/organize −3.0 (N=7); (iv) BRIEF inhibit −1.5, shift −0.3, emotional control −0.8, initiate −0.5, working memory −1.7, plan/organize −1.3, organization of materials −0.6, monitor −0.6 (N=101). Most patients had no shift in T-score category from baseline to last evaluation for each Achenbach CBCL subscale (between normal and borderline or clinical range [BCR], Fig 1) and BRIEF-P/BRIEF subscale (between normal and potential clinical significance [PCS], Fig 2). For all Achenbach CBCL subscales, the proportion of patients aged 1.5–5 and 6–16 years who changed from BCR to normal (range 6.3–21.9%, 12.7–17.6%, respectively) was numerically higher than for those who changed from normal to BCR (range 3.1–9.4%, 2.9–13.7%, respectively). Changes that occurred across BRIEF-P subscales were mostly from PCS to normal (range 14.3–28.6%). Across BRIEF subscales, similar proportions of patients changed from normal to PCS (range 8.0–16.8%) or from PCS to normal (range 7.1–13.3%). Treatment-emergent adverse events (TEAEs) were reported in 100% and 95.4% of patients aged 1.5–5 and 6–16 years, respectively (drug-related TEAEs 31.3%, 30.6%; serious TEAEs 21.9%, 27.8%; discontinuations due to TEAEs 6.3%, 9.3%; deaths [not considered drug-related] 3.1% [n=1], 1.9% [n=2]).
Conclusions: In this analysis, 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.
Funding: UCB Pharma-sponsored
Anti-seizure Medications