Add-on brivaracetam for epilepsy makes good in real-world practice

Long-term postmarketing data for adjunctive brivaracetam show that its use helps improve seizure control in patients with various epilepsy syndromes, even in those with prior exposure to levetiracetam. However, psychobehavioural adverse events (AEs) occur in one out of ten patients.

In a cohort of 262 children, adolescents, and adults who had initiated add-on brivaracetam, 33.1 percent reported >50-percent seizure reduction, including 10.9 percent who achieved seizure freedom, after 12 months. The retention rates were 61.1 percent after 1 year and 50.8 percent overall. [Epilepsia 2021;doi:10.1111/epi.17087]

“The observed responder rates within the first 12 months … in this study were in line with those reported by prior randomized controlled trials, and the overall high retention rate … underlined the good efficacy and tolerability of brivaracetam,” the investigators pointed out. [Epilepsia 2014;55:57-66; Epilepsia 2015;56:1890-1898; Epilepsia 2014;55:47-56; Neurology 2016;19:314-323]

“These findings were observed in a cohort in which 90 percent of patients had previous levetiracetam exposure, suggesting that levetiracetam treatment failure should not preclude brivaracetam introduction,” they added.

Although generally found to be safe and well-tolerated, brivaracetam was discontinued in 129 (49.2 percent) patients in total due to insufficient efficacy (n=63), psychobehavioural AEs (n=29), other adverse events (n=25), and other reasons (n=24).

The investigators acknowledged that the proportion of AE-related discontinuation was higher than described in the previous literature, chalking it up to the real-world setting of the present study. That is, the study was not limited by strict, a priori patient selection.

“When compared with other antiseizure medications that are prescribed in a similar setting, brivaracetam appeared equally or less disabling (discontinuation due to AEs: 30 percent for zonisamide, 46 percent for pregabalin, and 19 percent for levetiracetam),” they noted. [Epilepsy Res 2013;106:250-256]

Meanwhile, the psychobehavioural AEs, which were quite common, were postulated to be influenced by the brivaracetam activity on neurotransmitter systems, such as the γ-aminobutyric acid and serotoninergic systems. [Eur J Pharmacol 2011;16:36-44; Behav Neurol 2018;2018:2064027]

The study population had a mean age of 40 years (range, 5–81), and 49.2 percent were men. Diagnoses were focal epilepsy in 227 (87 percent) patients, genetic generalized epilepsy in 19 (7 percent), and other or unclassified epilepsy syndromes in 16 (6 percent). Only 26 (10 percent) patients had never received levetiracetam, whereas 133 (50.8 percent) were switched from levetiracetam.

Brivaracetam exposure lasted from 1 day to 5 years, with a median retention time of 1.6 years, which gave a total exposure time of 6,829 months (569 years). There were 133 patients who received brivaracetam at a mean dose of 222 mg, including 52 (39.1 percent) who exceeded the recommended upper dose of 200 mg.

Factors associated with better short-term response with brivaracetam were fewer concomitant antiseizure medications and switching from levetiracetam. No investigated parameters predicted positive long-term outcomes.

The study had several limitations, including the risks inherent to a retrospective design, a lack of a control group, and the fact that brivaracetam doses were not standardized in the present study, the investigators acknowledged.

“However, this real-world setting, which involved the uptitration of brivaracetam doses at the treating clinician’s discretion, represents one of the strengths of our study, as it reflects real-life clinical practices… Further prospective studies, including the evaluation of scales measuring quality of life and psychosocial inventories, are warranted to fully evaluate the long-term efficacy and tolerability of [the study drug],” they said.