Long-Term Follow-Up Study of Brivaracetam for Uncontrolled Focal Epilepsy

April 2022

Brivaracetam binds the synaptic vesicle protein 2A to control partial-onset seizures. First approved in 2016 in the United States and European Union as an adjunct to other antiepileptic drugs, it is now also approved as a monotherapy in the United States. These approvals were based on results from double-blind, placebo-controlled randomized clinical trials using intravenous or oral brivaracetam for the treatment of focal or generalized-onset seizures in adults.

In the new study, the investigators conducted a long-term follow-up trial for the participants in 2 of the earlier trials to determine the safety, tolerability, and maintenance of efficacy of brivaracetam as an adjunctive therapy. Patients in the previous clinical trials had uncontrolled focal or generalized-onset seizures that had not responded to other antiepileptic treatments. Those who completed the trials, regardless of whether they received placebo or brivaracetam, and were judged fit to receive brivaracetam as adjunctive therapy to another antiepileptic drug were allowed to enroll in the follow-up study.

Patients in the follow-up study received oral open-label brivaracetam along with their choice of other antiepileptic therapy. Adjustment of the brivaracetam dose was allowed as needed. The study included 767 patients from 5 continents. Only 2% had generalized-onset seizures; the rest had focal seizures. The primary outcome was safety and tolerability, and the secondary outcome was long-term efficacy.

During the follow-up study, 52% of patients discontinued brivaracetam. The most common reasons were lack of efficacy (21.4%) and adverse events (12.5%).

The safety and tolerability profile of brivaracetam were similar to that in previous trials. The investigators concluded that one-third of patients had adverse events related to brivaracetam, most commonly somnolence and dizziness. Of the 7 failed suicide attempts among patients during the study period, 2 are believed to be related to brivaracetam; however, scores on depression and anxiety scales did not change from baseline for most patients.

For the secondary outcome of efficacy, brivaracetam seemed to be efficacious for those who were able to stay on the drug. The median reduction in focal seizure frequency from baseline was 52%, and 52% of patients had a ≥50% reduction in seizure frequency by 12 months. Overall, 26% of patients went without a seizure for 6 months and 18% went without a seizure for 12 months. More than 40% of patients taking brivaracetam for ≥12 months reported improvement in quality-of-life questionnaires.

The investigators wrote that a limitation of the open-label efficacy trial design is that patients who do not respond to a drug will drop out, which causes an overestimate of long-term efficacy for the patients who remain in the trial. Another limitation of this trial was that the investigators were unable to analyze the generalized-onset seizure subset because of the small number of participants.

The investigators concluded that brivaracetam was safe and well-tolerated with long-term efficacy and noted that “these observations provide additional evidence for the use of adjunctive brivaracetam for the long-term treatment of patients with focal seizures.”


Toledo M, Brandt C, Quarato PP, et al. Long-term safety, efficacy, and quality of life during adjunctive brivaracetam treatment in patients with uncontrolled epilepsy: an open-label follow-up trial. Epilepsy Behav. 2021;118:107897.

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