Time Course of Treatment Emergent Adverse Events Potentially Associated with Behavioral Disorders During Adjunctive Brivaracetam Treatment of Adults with Focal Seizures
Abstract number :
V.070
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Year :
2021
Submission ID :
1825645
Source :
www.aesnet.org
Presentation date :
12/9/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:44 AM
Authors :
Svetlana Dimova, MD, PhD - UCB Pharma, Brussels; Pavel Klein, MD - Mid-Atlantic Epilepsy and Sleep Center; Cedric Laloyaux, PhD - UCB Pharma, Brussels; Xavier Nondonfaz, MD - UCB Pharma, Braine-l'Alleud; Florin Floricel, MD, PhD - UCB Pharma, Monheim am Rhein; Sami Elmoufti, MS - UCB Pharma, Raleigh; Kimford Meador, MD, FAAN, FAES, FRCPE - Department of Neurology and Neurological Sciences, Stanford University
Rationale: Previous analysis provided evidence that drug-related CNS treatment-emergent adverse events (TEAEs) occurred early in the course of adjunctive brivaracetam (BRV) treatment (initiated without titration) and then diminished over time (Meador KJ, et al. Epilepsy Behav 2020;111:107212). The objective of this analysis was to assess the time course of TEAEs potentially associated with behavioral disorders (BAEs) in adults with focal seizures during adjunctive BRV treatment, exploring the same dataset.
Methods: Post-hoc analysis of data pooled from three Phase III, double-blind, placebo (PBO)-controlled trials of adjunctive BRV in patients (aged ≥ 16 years) with focal seizures (N01252 [NCT00490035], N01253 [NCT00464269], N01358 [NCT01261325]). Incidence, prevalence, and discontinuation due to BAEs were assessed over time (12-week treatment) in patients randomized to BRV (50–200 mg/day without titration) or PBO.
Results: 803 patients randomized to BRV (50 mg/day n=200; 100 mg/day n=353; 200 mg/day n=250) and 459 randomized to PBO were included in the analysis (Safety Set). During 12-week treatment 4.6% (37/803) patients on BRV (50–200 mg/day) and 1.5% (7/459) on PBO reported ≥ 1 BAE; mainly of mild or moderate intensity (BRV: 89.2%; PBO: 85.7%) and with incidence similar in patients randomized to BRV 50, 100, and 200 mg/day (6.0%, 4.2%, 4.0%, respectively). Most BAEs began within the first 5 weeks of BRV treatment with highest incidence during week 2 (1.6%; median time: 13.0 days in both patients on BRV and PBO) which decreased thereafter (Fig. 1A). During BRV treatment the prevalence of BAEs increased from week 1 (1.0%) to week 5 (3.2%) and decreased slightly and remained generally stable from week 6 to week 12 (range 2.3–2.9%) (Fig. 1B). The most frequent BAEs (≥ 0.5% patients on BRV) were irritability (3.2% [PBO 0.7%]), aggression (0.5% [PBO 0.4%]), and agitation (0.5% [PBO 0]). The onset of irritability occurred mainly during the first 5 weeks of BRV treatment (median time: 13.5 days on BRV [PBO 19.0 days]) with prevalence increasing from week 1 (0.7%) to week 5 (2.4%) and stabilizing thereafter (range 2.2–2.4%) (Fig. 2). 0.7% (6/803) patients on BRV and 0.2% (1/459) on PBO discontinued treatment due to BAE (weeks 2−9; Fig. 1C), representing 16% (6/37) and 14% (1/7) of patients who reported ≥ 1 BAE on BRV and PBO, respectively. Of patients who reported ≥ 1 BAE, 81.1% (30/37) on BRV and 57.1% (4/7) on PBO continued in the open-label trial.
Conclusions: In this post-hoc analysis of Phase III trials of adjunctive BRV in adults with focal seizures, TEAEs potentially associated with behavioral disorders were reported in 4.6% patients, were not dependent on BRV dose, and had an onset mainly during the first 5 weeks of BRV treatment. Most of the patients who reported TEAEs potentially associated with behavioral disorders during the 12-week double-blind period continued long-term BRV treatment. These data further support the favorable tolerability profile of adjunctive BRV in adults with focal seizures.
Funding: Please list any funding that was received in support of this abstract.: UCB Pharma-funded.
Anti-seizure Medications