Add-on brivaracetam safe, cuts focal seizure frequency

Adjunctive therapy with brivaracetam (BRV) is well tolerated and yields substantial reduction in focal seizure frequency regardless of the number or type of concomitant antiseizure medications (ASMs) used, as reported in a study.

In a pooled analysis of three phase III trials with a treatment duration of 12 weeks, adult patients with focal seizures who received therapeutic doses of BRV (50–200 mg/day) in addition to one (n=181) or two (n=557) ASMs had similar incidences of treatment-emergent adverse events (TEAEs; 68.0 percent and 66.4 percent, respectively), drug-related TEAEs (41.4 percent and 41.5 percent), and TEAEs leading to discontinuation (6.6 percent and 5.4 percent). [Epilepsia 2022;doi:10.1111/epi.17304]

Likewise, among patients who received placebo, there was no notable difference in safety between those with one (n=95) or two (n=331) concomitant ASMs. TEAEs occurred in 60.0 percent and 60.7 percent, drug-related TEAEs in 32.6 percent and 30.2 percent, and TEAEs leading to discontinuation in 2.1 percent and 4.5 percent, respectively.

“The incidences of TEAEs, drug-related TEAEs, and TEAEs leading to discontinuation by specific concomitant ASM (carbamazepine, lamotrigine, oxcarbazepine, valproate) were similar to the overall incidences in [BRV-treated] patients taking one concomitant ASM,” according to the investigators.

Overall, the most common TEAEs during adjunctive BRV (50–200mg/day) treatment were somnolence, fatigue, dizziness, and headache. Meanwhile, insomnia, anxiety, and depression were the most frequent psychiatric TEAEs.

“Considering that AEs were the most common reason for BRV discontinuation, these data may suggest that there was no impact of the number and type of baseline ASMs on the discontinuation of BRV due to intolerable TEAEs,” the investigators noted.

“Psychiatric TEAEs and TEAEs associated with behavioural disorders are often associated with the use of ASMs and can lead to early discontinuation, poor drug adherence, and suboptimal dosing. In this pooled analysis, the incidence of psychiatric TEAEs in patients randomized to BRV (50–200mg/day) were similar whether they were taking one or two concomitant ASMs and did not increase with increasing BRV doses,” the investigators noted. [Epilepsy Behav 2017;76:24-31]

Efficacy

Adjunctive BRV also demonstrated efficacy in patients taking one or two ASMs concomitantly. The corresponding 50-percent responder rates were numerically higher in the BRV group (42.3 percent and 36.8 percent, respectively) than in the placebo group (18.3 percent vs 19.5 percent, respectively).

Furthermore, patients taking one or two ASMs in the BRV group had numerically higher 100-percent responder rates (9.1 percent and 4.5 percent, respectively) and seizure freedom (6.9 percent and 3.7 percent) than those in the placebo group (1.1 percent and 0.3 percent; 1.1 percent and 0 percent).

BRV also showed superiority over placebo across patients taking concomitant carbamazepine, lamotrigine, oxcarbazepine, or valproate in terms of all efficacy endpoints.

The safety and efficacy data of BRV “were supported by a logistic regression analysis showing no impact of the number and type of baseline ASM on the trial discontinuation rate,” the investigators said.

However, the investigators advised caution in interpreting these data due to the presence of several study limitations, such as the small sample size of individual subgroups.

“Different pharmacokinetic and pharmacodynamic interactions are possible when two or more ASMs are used concomitantly, which may affect the interpretation of the data. Therefore, the current analysis was focused on patients on one specific concomitant ASM, which provided a low sample size,” the investigators said.

Nevertheless, the findings, when taken together, “further support the good tolerability and efficacy profile of adjunctive BRV in patients with focal seizures, and its compatibility of use with other ASMs,” they added.