Authors :
Allison Little, PharmD – UCB Pharma, Smyrna, Georgia, US; Dimitrios Bourikas, PhD – UCB Pharma, Alimos, Greece; Fiona Brock, MSc – UCB Pharma, Slough, UK; Prashant Dongre, MD – UCB Pharma, Smyrna, Georgia, US; Sami Elmoufti, MSc – UCB Pharma, Morrisville, North Carolina, US; Iryna Leunikava, MSc – UCB Pharma, Monheim am Rhein, Germany; Anne-Liv Schulz, MD – UCB Pharma, Monheim am Rhein, Germany
Rationale: Limited evidence is available on the effectiveness and tolerability of brivaracetam (BRV) in older (≥65 years) patients with focal onset seizures treated in real-life settings, including reasons for initiating BRV in this population.
Methods: Post hoc analysis of final data from two 12-month, prospective, noninterventional studies of patients initiating BRV in Europe (EP0077/NCT02687711) and the United States (EP0088). Patients (≥18 years) with focal onset seizures, without BRV treatment prior to study entry, ≥1 lifetime antiseizure medication (ASM; ASMs either stopped before or ongoing at BRV initiation), and ≥1 BRV dose during the study were included in this analysis. Patients received BRV as prescribed by their physician and were followed for up to 12 months from BRV initiation. Outcomes were assessed for subgroups of patients by age (< 65 years and ≥65 years). BRV retention at 12 months was defined as patients who remained in the study and were on BRV treatment for at least 12 months (≥330 days in EP0077, ≥309 days in EP0088) after BRV initiation. Other reported outcomes include Kaplan-Meier estimated time to discontinuation of BRV/early study termination and incidence of treatment-emergent adverse events (TEAEs) during the study.
Results: Of 720 patients included in the analysis, 660 (91.7%) were aged < 65 years and 60 (8.3%) were ≥65 years (Table 1). The most common reason for BRV initiation (more than one reason allowed) was lack of efficacy of current ASM in 550 (83.3%) and 45 (75.0%) patients aged < 65 years and ≥65 years, respectively, followed by behavioral adverse events (127 [19.2%] and 16 [26.7%]) and other intolerance to current ASM (105 [15.9%] and 7 [11.7%]). Median BRV dose at initiation was 100 mg/day in patients aged < 65 years and 50 mg/day in patients aged ≥65 years. The median BRV dose at last assessment and the mean modal dose were 150 mg/day in patients aged < 65 years and 100 mg/day in those aged ≥65 years. Median BRV treatment duration was 11.7 and 11.8 months in patients aged < 65 years and ≥65 years, respectively. BRV retention at 12 months was 57.6% and 60.0% for patients aged < 65 and ≥65 years, respectively. The estimated probability of patients not discontinuing BRV/terminating the study by day 360 (Kaplan-Meier analysis) for < 65 years vs ≥65 years for any reason was 61% vs 62% (Figure 1A); due to lack of efficacy was 86% vs 90% (Figure 1B), and due to TEAEs was 74% vs 75% (Figure 1C). The overall tolerability profile during BRV treatment was similar between age groups, with patients aged < 65 years and ≥65 years, respectively, reporting any TEAEs (43.5% and 41.7%), drug-related TEAEs (25.8% and 26.7%), behavioral TEAEs (8.0% and 6.7%), and discontinuing due to TEAEs (23.5% and 23.3%).
Conclusions: This analysis showed similar effectiveness and tolerability of BRV in adults aged < 65 years and ≥65 years in a real-world clinical setting, further supporting the effectiveness and favorable tolerability profile of BRV regardless of patient’s age.
Funding: UCB Pharma-sponsored