Introduction

Brivaracetam (BRV; 50–200 mg/day) has shown clinically relevant seizure freedom and reductions in seizure frequency, with a low incidence of adverse events (AEs) and low discontinuation rates due to AEs. BRV is approved as a treatment for focal-onset seizures with or without secondary generalisation. However, real-world evidence of BRV has been restricted in scope, location, and patient numbers.

Aim

To analyze existing real-world data on effectiveness and tolerability of BRV in routine practice across specific patient groups

Patient Profile

• 1644 patients with epilepsy initiated on BRV

Method

Study Design

• Pooled analysis of individual patient records from multiple independent noninterventional, international retrospective studies, that used clinical chart review cohorts of patients who initiated BRV in clinical practice.

  Endpoints

• Efficacy outcomes: ≥ 50% reduction from baseline in seizure frequency, seizure freedom, continuous seizure freedom and BRV retention at 3, 6, and 12 months
• Safety and tolerability outcomes: BRV discontinuation due to tolerability reasons, and incidence of treatment-emergent adverse events (TEAEs) since prior visit, severity of TEAEs
• Subgroups analyzed: seizure type recorded at baseline; number of prior antiseizure medications (ASMs) at index; use of BRV monotherapy versus polytherapy ; for patients who switched from levetiracetam to BRV versus patients who switched from other ASMs to BRV; and for patients with focal-onset seizures and a BRV dose of ≤ 200 mg/day used as add-on at index

  Results

  Efficacy

• BRV achieved ≥ 50% seizure reduction in 32.1%, 36.7%, 36.9%, seizure freedom rates in 22.4%, 17.9%, 14.9% and continuous seizure freedom rates in 22.4%, 15.7% and 11.7% of patients at 3, 6, and 12 months, respectively (Figure 1)
• Overall, a high BRV therapy retention was noted (89.4%, 79.8%, 71.1% at 3, 6 and 12 months, respectively); 50% of patients remained on BRV at 1464 days since BRV initiation.
• Outcomes of >50% seizure reduction, seizure freedom, and continuous seizure freedom rates at 12 months in patients with focal-onset seizures without secondary generalisation at baseline were 40.4%, 12.1%, 7.5%, resp., in those with secondary generalisation were 34.0%, 18.1%, 16.7% and in those with generalised-onset seizures were 24.0%, 18.8%, 15.6%

   

  Figure 1: Outcomes at 12 months with BRV adjunctive therapy in epilepsy patients

  

  Safety 

• Overall, 33.6% patients discontinued BRV during the whole study follow-up.
• TEAEs since prior visit were reported in 25.6%, 14.2%, and 9.3% of patients (severe TEAEs in 12.9%, 7.0%, and 6.4%) at 3, 6, and 12 months, respectively
• BRV discontinuation was attributed to lack of effectiveness (44.6%), tolerability (35.0%), or both reasons (13.4%)
• BRV discontinuations were similar in the seizure type subgroups (32.2% in focal-onset seizures without secondary generalisation; 33.7% in focal-onset seizures with secondary generalisation; 31.1% in generalised-onset seizures)
• Lower TEAEs were reported in patients with generalised-onset seizures (4%) as compared to patients with focal-onset seizures without secondary generalisation (10%) or with secondary generalisation (9.7%) at 12 months
• BRV discontinuation was seen in 27.4%, 31.1%, 30.3%, and 41.4% of patients in the 0–1, 2–3, 4–6, and ≥7 prior ASMs subgroups, respectively
• As the number of prior ASMs increased, BRV discontinuation due to lack of effectiveness increased (from 27.3% in 0–1 prior ASM subgroup to 54% in ≥7 prior ASMs subgroup), however discontinuation due to tolerability decreased (from 43.9% in 0–1 prior ASM subgroup to 28.1% in ≥7 prior ASMs subgroup)
• Higher TEAE incidence since the prior visit was seen in patients with 4–6 and ≥7 prior ASMs (11.5% and 10.0%, respectively) versus patients with 0–1 and 2–3 prior ASMs (7% and 7.4%, respectively)
• BRV discontinuation was higher in polytherapy (33.9%) vs BRV monotherapy (24.4%)
• Numerically lower TEAE incidence was seen in patients on BRV monotherapy versus polytherapy (3.8% vs 9.5%)
• BRV discontinuation was seen in 32% of patients who switched from levetiracetam and 35.8% of patients who switched from other ASMs
• In patients with focal‑onset seizures (BRV dose ≤ 200 mg/day used as add‑on at index), TEAEs since prior visit were reported in 26.4%, 15.3%, and 9.9% of patients at 3, 6, and 12 months, respectively

• BRV monotherapy patients had a shorter epilepsy duration (median 9 vs. 18 years) and a lower number of prior ASMs (3 vs. 5) versus those on polytherapy
• Patients on BRV monotherapy had numerically higher seizure freedom (58.1%, 34.5%, 36%) and continuous seizure freedom rates than patients on polytherapy (58.1%, 31%, 28%) at 3, 6, and 12 months.
• BRV retention was similar in patients on BRV monotherapy versus polytherapy
• In patients with focal‑onset seizures, BRV (≤ 200 mg/day used as add‑on at index) achieved ≥ 50% seizure reduction in 31.4%, 36.8%, and 38.1% of patients, seizure freedom in 20.8%, 17.1%, and 14.4%, and continuous seizure freedom in 20.8%, 15.2%, and 11.2% with BRV retention in 89.6%, 79.6%, and 71.2% of patients at 3, 6, and 12 months, respectively

Conclusion

• BRV was effective and well tolerated in routine clinical practice in drug-resistant epilepsy patients
• The study also showed its efficacy and safety among patients on BRV monotherapy, different types of seizures, and patients who had switched to BRV from other ASMs, including levetiracetam

CNS Drugs 2023; 37: 819–35