First clinical postmarketing experiences in the treatment of epilepsies with brivaracetam: a retrospective observational multicentre study

Abstract

ObjectivesBrivaracetam (BRV) is the latest approved antiepileptic drug and acts as a synaptic vesicle protein 2A ligand. The aim of the present study was to evaluate the efficacy and tolerability of BRV in the clinical setting.DesignRetrospective, observational multicentre study.SettingWe retrospectively collected clinical data of patients who received BRV in 10 epilepsy centres using a questionnaire that was answered by the reporting neurologist.ParticipantsData of 615 epilepsy patients treated with BRV were included in the study.Primary and secondary outcome measuresEfficacy regarding seizure frequency and tolerability of BRV were evaluated. Descriptive statistics complemented by X2 contingency tests and effect sizes were performed.ResultsOverall, 44% of the patients had a decreased, 38% a stable and 18% an increased seizure frequency. 17% of patients achieved seizure freedom after initiation of BRV. The seizure frequency decreased in 63% of 19 patients with BRV monotherapy. 27% reported adverse effects, but only 10% of patients with monotherapy. Brivaracetam was significantly more often associated with decreased seizure frequency in levetiracetam (LEV) naïve patients (p=0.012), but BRV also led to a decreased seizure frequency in 42% of patients who had been treated with LEV before, including 17% of patients who were completely seizure free. Adverse effects under LEV improved in 62% and deteriorated in 2% of patients after the switch to BRV. At latest follow-up (mean±SD = 26.3±6.5 months), 68% were still on BRV.ConclusionsThe present study shows that results of the phase III studies on BRV match data from real life clinical settings. Brivaracetam seems to be a useful alternative in patients who have suffered adverse effects while taking LEV.

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

“…The most frequently observed AEs were somnolence, vertigo, fatigue and headache, which substantially overlap the profile of adverse effects of the majority of the ASMs [37]; nervousness and agitation were reported by 6% of patients and were the most common psychiatric AEs. These data confirmed the overall favourable tolerability profile of BRV when added to concomitant ASMs, and matched the already available evidence from both randomized and open-label studies [13,[21][22][23][24][25][26][27][28]. A slow-escalation dosing regimen may represent a useful strategy to avoid or minimize adverse effects as somnolence and fatigue.…”

“…In the cohort of patients included in the BRIVAFIRST who have a long disease duration, a considerable number of previously failed ASMs, and a high number of ongoing ASMs, the rates of seizure freedom and seizure response at 12-month follow-up were 16% and 37%, respectively. These figures indicate the efficacy of BRV to control seizures when added to the pre-existing therapeutic regimen in everyday clinical practice in patients with difficult-to-treat epilepsy, and confirm previous evidence [21][22][23][24][25][26][27][28]. In line with other ASMs [29,30], an inverse relationship between response to adjunctive BRV and the number of lifetime medications was observed, confirming that the higher the number of failed treatments, the lower the likelihood that the patient may benefit from subsequent interventions [31].…”

“…During the 1-year study period, the overall rate of treatment discontinuation was about 25%, which was similar to that observed in other studies focusing on BRV and newer ASMs in clinical practice, including eslicarbazepine, perampanel, and lacosamide [21][22][23][24][25][26][27][28][29][34][35][36]. The main reason for drug withdrawal was inadequate efficacy, and BRV was interrupted within the first 3 months of treatment in almost half of the cases.…”

Effectiveness and Safety of Brivaracetam in Children

“…The safety and tolerability profile in children are similar to adults [2,3]. We noted greater than 50% seizure reduction in 36%, seizure-free in 10%, unchanged seizure frequency in 47%, increased seizure frequency in 5.2% compared to 44%, 17%, 38%, and 18%, respectively reported in adults [4]. To conclude, Brivaracetam adjunctive treatment is well tolerated, safe, and effective in children.…”

Critical Appraisal of Cenobamate as Adjunctive Treatment of Focal Seizures in Adults

“…There is a suspect that all ASMs, as a class and across all ranges of indications, may be associated with a small increment of suicidal thoughts or behaviour 32 even though a more recent analysis failed to confirm this finding. 33 In the open-label CNB study, 16 [34][35][36][37][38] are still not available. Hence, we do not know how many drug-resistant patients with focal epilepsies that achieved seizure freedom over few months in the randomized, double-blind studies will keep on without seizures over the years.…”