Data out to 11 years suggest that individualized doses of brivaracetam (Briviact; UCB Pharma) are safe and effective in reducing focal and primary generalized seizures.
Terence J. O'Brien, MBBS, MD
New analysis suggests that long-term use of brivaracetam (Briviact; UCB Pharma) is well-tolerated and safe for adults with epilepsy in individualized doses ≤200 mg/d, with stable efficacy, based on data of up to 11 years of follow-up. More than half of those with focal seizures in the study experienced ≥50% reduction in focal seizure frequency, while 30% experienced continuous seizure freedom for ≥6 months.1
All told, over the course of the study period, 667 patients aged 16 years and older from brivaracetam clinical development trials (NCT00175825, NCT00490035, NCT00464269, or NCT00504881) experienced treatment emergent adverse events (AEs) at a rate of 91.2% (n = 608)—of the 652-patient focal seizures group, AEs occurred in 91.3% (n = 595)—with only 14.8% (n = 99) discounting treatment due AEs.
Drug-related AEs occurred in 56.7% (n = 378) of patients, and serious AEs in 22.8% (n = 152). The most common AEs in the focal seizures group, at a rate of ≥15% were headache (25.3%; n = 165) and dizziness (21.9%; n = 143).
The study was conducted by a group of investigators, including Terence J. O'Brien, MBBS, MD, head, Departments of Neuroscience and Medicine, and deputy head of school, Central Clinical School, Monash University; program director, Alfred Brain; and director of neurology, and deputy director of research, Alfred Health, and included a safety dataset with 667 patients (focal seizures, 97.8% [n = 652]; primary generalized seizures [PGS], 2.2% [n = 15]) and an efficacy set with 648 patients with focal seizures and 15 patients with PGS. Overall, 49.2% (n = 328) of patients had ≥48 months of exposure.
“During extended treatment, brivaracetam was generally safe and well-tolerated, with only a small proportion of patients permanently discontinuing brivaracetam due to TEAEs,” O’Brien and colleagues wrote. “This could be related to the flexible-dose trial design, which allowed dose adjustment of brivaracetam and concomitant antiepileptic drugs [AEDs], as well as addition and discontinuation of concomitant AEDs to optimize tolerability.”
They also noted that the incidence of AEs was slightly elevated in the initial 3 months of treatment, declining in the following time intervals—which they described as expected. “Patients who received placebo in the previous trials received brivaracetam for the first time in this trial, and patients who may have been on a lower dose of brivaracetam in the previous trials received an up-titration when they transitioned to this long-term follow-up trial,” they wrote.
As for efficacy, the focal seizures group experienced a median reduction from baseline 28-day seizure frequency of 57.3%, with 55.6% (n = 360) of patients reporting a ≥50% reduction in seizures. The 6-month and 12-month seizure freedom rates were 30.3% (n = 170) and 20.3% (n = 114), respectively. Throughout the 108-week assessment of efficacy, the mean (standard deviation [SD]) reduction in seizures ranged from 47.3% (SD, 57.9) in months 1—12 (n = 485) to 67% (SD, 33.2) in months 1–108 (n = 83).
The mean improvement from baseline in Patient Weighted Quality of Life in Epilepsy Inventory total score (in the efficacy set) was 5.7 (SD, 16.1; d = 0.35) at month 12 and 6.5 (SD, 18.0; d = 0.36) at month 24. The average changes from baseline in Hospital Anxiety and Depression Scale scores at last value in the year evaluation were reduced by 0.7 (SD, 4.3) for anxiety and 0.2 (SD, 4.4) for depression, overall.
“Limitations of this trial include the open-label, single-arm design and the small number of patients with PGS enrolled, which does not allow meaningful conclusions to be drawn for those patients,” O’Brien and colleagues acknowledged. “Although the flexible-dose trial design limits the conclusions that can be drawn regarding the relationship between brivaracetam dose and efficacy, individualized dosing is closer to clinical practice than fixed dosing.”