Adjunctive Brivaracetam in Focal Epilepsy: Real-World Evidence from the BRIVAracetam add-on First Italian netwoRk STudy (BRIVAFIRST)

Abstract

Background In randomized controlled trials, add-on brivaracetam (BRV) reduced seizure frequency in patients with drugresistant focal epilepsy. Studies performed in a naturalistic setting are a useful complement to characterize the drug profile. Objective This multicentre study assessed the effectiveness and tolerability of adjunctive BRV in a large population of patients with focal epilepsy in the context of real-world clinical practice. Methods The BRIVAFIRST (BRIVAracetam add-on First Italian netwoRk STudy) was a retrospective, multicentre study including adult patients prescribed adjunctive BRV. Patients with focal epilepsy and 12-month follow-up were considered. Main outcomes included the rates of seizure-freedom, seizure response (≥ 50% reduction in baseline seizure frequency), and treatment discontinuation. The incidence of adverse events (AEs) was also considered. Analyses by levetiracetam (LEV) status and concomitant use of strong enzyme-inducing antiseizure medications (EiASMs) and sodium channel blockers (SCBs) were performed. Results A total of 1029 patients with a median age of 45 years (33-56) was included. At 12 months, 169 (16.4%) patients were seizure-free and 383 (37.2%) were seizure responders. The rate of seizure freedom was 22.3% in LEV-naive patients, 7.1% in patients with prior LEV use and discontinuation due to insufficient efficacy, and 31.2% in patients with prior LEV use and discontinuation due to AEs (p < 0.001); the corresponding values for ≥ 50% seizure frequency reduction were 47.9%, 29.7%, and 42.8% (p < 0.001). There were no statistically significant differences in seizure freedom and seizure response rates by use of strong EiASMs. The rates of seizure freedom (20.0% vs. 16.6%; p = 0.341) and seizure response (39.7% vs. 26.9%; p = 0.006) were higher in patients receiving SCBs than those not receiving SCBs; 265 (25.8%) patients discontinued BRV. AEs were reported by 30.1% of patients, and were less common in patients treated with BRV and concomitant SCBs than those not treated with SCBs (28.9% vs. 39.8%; p = 0.017). ConclusionThe BRIVAFIRST provided real-world evidence on the effectiveness of BRV in patients with focal epilepsy irrespective of LEV history and concomitant ASMs, and suggested favourable therapeutic combinations.

Third-Generation Antiseizure Medications for Adjunctive Treatment of Focal-Onset Seizures in Adults: A Systematic Review and Network Meta-analysis

“…BRV50 brivaracetam 50 mg/day, BRV100 brivaracetam 100 mg/day, BRV200 brivaracetam 200 mg/day, CNB200 cenobamate 200 mg/day, CNB400 cenobamate 400 mg/day, ESL800 eslicarbazepine acetate 800 mg/day, ESL1200 eslicarbazepine acetate 1200 mg/day, LCM200 lacosamide 200 mg/day, LCM400 lacosamide 400 mg/day PBO placebo, PER4 perampanel 4 mg/day, PER8 perampanel 8 mg/day, PER12 perampanel real-world clinical practice is significantly reduced by the concomitant use of an ASM acting as an SCB [48]. Although to date, there are no experimental data about any advantageous combinations of BRV with other ASMs, additive or synergic pharmacodynamic interactions between BRV and one or more compounds acting on voltage-gated sodium channels may exist and need to be specifically addressed.…”

“…The good tolerability profile of BRV versus the other third-generation ASMs has been already demonstrated in prior indirect comparisons [ 46 , 47 ]. In this regard, it is interesting that more than three-quarters of participants assigned to BRV treatment in the RCTs were taking sodium channel blockers (SCBs) as concomitant ASMs, and the risk of TEAEs in patients treated with BRV within the context of real-world clinical practice is significantly reduced by the concomitant use of an ASM acting as an SCB [ 48 ]. Although to date, there are no experimental data about any advantageous combinations of BRV with other ASMs, additive or synergic pharmacodynamic interactions between BRV and one or more compounds acting on voltage-gated sodium channels may exist and need to be specifically addressed.…”

“…Studies with shorter double-blind treatment periods may have underestimated the occurrence of TEAEs compared to those with longer time frames available for tolerability assessment, and a higher burden of concomitant ASMs may have resulted in an increased frequency of TEAEs. Further, the lack of efficacy and tolerability data according to the mechanism of action of concomitant ASMs prevents to explore or confirm potential favourable or unfavourable drug interactions and combinations [ 48 , 56 ].…”

Sustained seizure freedom with adjunctive brivaracetam in patients with focal onset seizures

“…BRIVAFIRST (BRIVAracetam add‐on First Italian netwoRk STudy) was a retrospective study conducted across 63 Italian centers 2 . Adult patients (age ≥ 16 years) attending participating centers who were prescribed BRV (March 2018 to March 2020) and were on stable treatment with ≥1 ASM during the prior 90 days were retrospectively identified.…”

“…BRIVAFIRST (BRIVAracetam add-on First Italian net-woRk STudy) was a retrospective study conducted across 63 Italian centers. 2 Adult patients (age ≥ 16 years) attending participating centers who were prescribed BRV (March 2018 to March 2020) and were on stable treatment with ≥1 ASM during the prior 90 days were retrospectively identified. Only patients with focal epilepsy, 12-month follow-up after initiating BRV, and at least one seizure during the 3 months before introducing BRV were included in the current analysis.…”