Authors :
Presenting Author: Dimitrios Bourikas, PhD – UCB Pharma, Alimos, Greece
Najla Dickson, MD – UCB Pharma, Morrisville, NC, USA; Christine De La Loge, MSc – PCOM Analytics, Avallon, France; Svetlana Dimova, MD, PhD – UCB Pharma, Brussels, Belgium; Sami Elmoufti, MSc – UCB Pharma, Morrisville, NC, USA; Brian Moseley, MD – UCB Pharma, Morrisville, NC, USA; Lieven Lagae, MD, PhD – Pediatric Neurology, University Hospitals Leuven, Member of EpiCARE ERN, Belgium
Rationale:
To evaluate behavioral and executive functioning during long-term adjunctive brivaracetam (BRV) treatment in pediatric patients with focal-onset seizures with and without cognitive or learning comorbidities (CLC).
Methods:
A post hoc analysis of a phase 3, open-label, follow-up trial (N01266/NCT01364597) was conducted. Patients with focal-onset seizures (aged ≥1 month to <17 years at core trial entry) received ≤5 mg/kg/day BRV (tablet/oral solution; max ≤200 mg/day). Subgroup analyses were performed for patients with/without ongoing CLC at baseline (BL). Cognitive and behavioral outcomes were evaluated with Achenbach CBCL 1.5–5/6–18 (patients aged 1.5–5/6–16 years) syndrome scales and BRIEF (patients aged 5–16 years) indices. BRIEF-P data are not reported due to the small number of patients aged two to five years (N=7).
Results:
CBCL 1.5−5 T-Score categories at BL were borderline or clinical range (BCR) in ≥50% of patients with (N=14) and without (N=18) CLC for attention problems (57.1%, 50.0%, respectively) and withdrawn for patients with CLC (64.3%) (Fig 1A).
Mean changes in CBCL 1.5−5 syndrome raw scores from BL to last evaluation were generally close to 0 in patients with CLC, reflecting stability overall, while those without CLC had small numerical improvements in all syndrome scores (Fig 1B). From BL to last evaluation, most patients with/without CLC (≥50.0%/≥72.2%) had no shift in T-Score category for each subscale; and T-Score reliable change index (RCI) showed most patients (≥64.3%/≥83.3%) were stable or improved. CBCL 6−18 T-Score categories at BL were BCR in ≥50% of patients with CLC (N=47) for attention problems (66.0%) and social problems (63.8%); corresponding values for patients without CLC (N=55) were 34.5% and 40.0% (Fig 1C).
From BL to last evaluation, both subgroups had numerical improvements in the mean change in raw scores for most scales (Fig 1D); most patients with/without CLC (≥66.0%/≥69.1%) had no shift in T-Score category for each subscale; and RCI showed most patients (
≥68.1%/≥63.6%) were stable or improved. For BRIEF, a numerically higher proportion of patients with vs without CLC had BL T-Score categories in the potential clinical significance (PCS) category for Behavioral Regulation Index (BRI), Metacognition Index (MI) and Global Executive Composite (GEC) (Fig 2A). From BL to last evaluation, patients with CLC had an increase in BRI and no change in MI, leading to a small numerical increase in GEC; patients without CLC had small numerical improvements in BRI, MI and GEC (Fig 2B); most patients with/without CLC had no shift in T-Score category for BRI, MI and GEC (≥84.2%/≥69.6%); and RCI showed most patients (≥60.0%/≥77.8%) were stable or improved.
Conclusions:
During long-term adjunctive BRV treatment in pediatric patients with focal-onset seizures, most behavioral and executive functioning scores were stable or slightly improved in patients with and without CLC, with higher improvements in patients without CLC.
Funding:
UCB Pharma-sponsored