Effectiveness and Tolerability of Brivaracetam by Number of Lifetime Antiseizure Medications in Adults with Focal Onset Seizures: Pooled Data From Two Real-world Studies

Abstract-Text (inklusive Referenzen und Bildunterschriften)

Question: The clinical response to newly administered antiseizure medications (ASMs) can be affected by ASM treatment history (Schiller Y, Najjar Y. Neurology 2008;70[1];54-65). We analyzed the impact of number of lifetime ASMs on effectiveness and tolerability of brivaracetam (BRV) in adults with focal-onset seizures in a real-world clinical setting.

Methods: Pooled analysis of data from two 12-month, prospective, noninterventional studies in patients initiating BRV in Europe (EP0077/NCT02687711) and the United States (EP0088). Patients received BRV as prescribed by their physician and were followed for up to 12 months from BRV initiation. Post hoc analysis included patients (≥18 years) with focal onset seizures and ≥1 lifetime ASM at the time of BRV initiation. Outcomes were assessed for all patients and for subgroups of patients by number of lifetime ASMs (ASMs stopped before BRV initiation or ongoing at BRV initiation).

Results: Of 720 patients included in the analysis, 101 (14.0%), 165 (22.9%), 119 (16.5%), and 335 (46.5%) had 1–2, 3–4, 5–6, and ≥7 lifetime ASMs, respectively. At baseline, patients with fewer lifetime ASMs had a higher age at epilepsy diagnosis and shorter time since epilepsy diagnosis (Table 1). In all lifetime ASM subgroups, the main reason for BRV initiation was lack of efficacy of current treatment (range: 73.3% [1–2 ASMs] to 89.0% [≥7 ASMs]) (Table 1). The median BRV modal dose was 100 mg/day in patients with 1–2, 3–4, and 5–6 lifetime ASMs, and 150 mg/day in patients with ≥7 lifetime ASMs. BRV retention at 12 months was 68.3%, 66.1%, 55.5%, and 51.3% in patients with 1–2, 3–4, 5–6, and ≥7 lifetime ASMs, respectively (Figure 1A). Patients with 1–2 and 3–4 lifetime ASMs were less likely to discontinue BRV or terminate the study compared to those with ≥5 lifetime ASMs (Kaplan-Meier estimates; Figure 1B). Patients with fewer lifetime ASMs were less likely to discontinue BRV due to lack of efficacy or due to TEAEs. 12-month seizure freedom since baseline was 20.0% (n=85), 14.8% (n=142), 6.8% (n=88), and 2.7% (n=294) in patients with 1–2, 3–4, 5–6, and ≥7 lifetime ASMs, respectively. TEAEs were reported in 26.7%, 37.0%, 46.2%, and 50.4% of patients with 1–2, 3–4, 5–6, and ≥7 lifetime ASMs; 10.9%, 17.6%, 29.4%, and 33.1% had drug-related TEAEs; and 13.9%, 17.0%, 21.8%, and 30.1% discontinued due to TEAEs (Figure 1C).

Conclusions: In this post hoc analysis of data from two real-world studies, patients with fewer lifetime ASMs upon initiation of BRV had numerically higher retention, and numerically lower incidences of TEAEs and discontinuations due to TEAEs. 12-month effectiveness and tolerability were highest in patients with 1–2 lifetime ASMs before BRV initiation. Effectiveness of BRV was also observed in patients with ≥7 ASMs, with over half of such patients remaining on BRV for ≥12 months.

Funding: UCB Pharma-sponsored.