Adjunctive Brivaracetam in Older Patients with Focal Seizures: Evidence from the BRIVAracetam add‑on First Italian netwoRk Study (BRIVAFIRST)

Abstract

Background The management of epilepsy in older adults has become part of daily practice because of an aging population. Older patients with epilepsy represent a distinct and more vulnerable clinical group as compared with younger patients, and they are generally under-represented in randomized placebo-controlled trials. Real-world studies can therefore be a useful complement to characterize the drug’s profile. Brivaracetam is a rationally developed compound characterized by high-affinity binding to synaptic vesicle protein 2A and approved as adjunctive therapy for focal seizures in adults with epilepsy. Objective The aim of this study was to assess the 12-month effectiveness and tolerability of adjunctive brivaracetam in older patients (≥65 years of age) with epilepsy treated in a real-world setting. Methods The BRIVAFIRST (BRIVAracetam add-on First Italian netwoRk STudy) was a 12-month retrospective multicenter study including adult patients prescribed adjunctive brivaracetam. Effectiveness outcomes included the rates of seizure response (≥50% reduction in baseline seizure frequency), seizure freedom, and treatment discontinuation. Safety and tolerability outcomes included the rate of treatment discontinuation due to adverse events and the incidence of adverse events. Data were compared for patients aged ≥65 years of age (‘older’) vs those aged <65 years (‘younger’). Results There were 1029 patients with focal epilepsy included in the study, of whom 111 (10.8%) were aged ≥65 years. The median daily dose of brivaracetam at 3 months was 100 [interquartile range, 100–175] mg in the older group and 100 [100–200] mg in the younger group ( p = 0.036); it was 150 [100–200] mg in both groups either at 6 months ( p = 0.095) or 12 months ( p = 0.140). At 12 months, 49 (44.1%) older and 334 (36.4%) younger patients had a reduction in their baseline seizure frequency by at least 50% ( p = 0.110), and the seizure freedom rates were 35/111 (31.5%) and 134/918 (14.6%) in older and younger groups, respectively ( p < 0.001). During the 1-year study period, 20 (18.0%) patients in the older group and 245 (26.7%) patients in the younger group discontinued brivaracetam ( p = 0.048). Treatment withdrawal because of insufficient efficacy was less common in older than younger patients [older: n = 7 (6.3%), younger: n = 152 (16.6%); p = 0.005]. Adverse events were reported by 24.2% of older patients and 30.8% of younger patients ( p = 0.185); the most common adverse events were somnolence, nervousness and/or agitation, vertigo, and fatigue in both study groups. Conclusions Adjunctive brivaracetam was efficacious, had good tolerability, and n...

Brivaracetam as Early Add-On Treatment in Patients with Focal Seizures: A Retrospective, Multicenter, Real-World Study

“…The burden of concomitant medications and the baseline seizure frequency can act as surrogate markers of the intrinsic disease severity, and the inverse relationship found between the response to adjunctive BRV and these baseline characteristics is consistent with prior studies [12,29]. Likewise, age was an independent predictor of sustained seizure frequency reduction, with older age being associated with a greater likelihood to achieve SSR and SSF; the better response to BRV in older versus younger patients is also in line with prior evidence [5,7,30]. Remarkably, ASMs are generally found to be more efficacious in elderly than younger patients when outcomes are stratified by age, and differences across the age groups can largely be explained by differences in baseline characteristics of participants [31,32].…”

“…Most real-world research on BRV has focused on refractory epilepsy and only a few studies have provided preliminary insights about BRV use in special populations [4][5][6] and in the early stages of treatment [7]. There is, hence, little information about the effectiveness of BRV when it is administered as a first or second add-on therapy.…”

Sustained seizure freedom with adjunctive brivaracetam in patients with focal onset seizures

“…The higher rates of SSF and SSR observed in elderly patients also agree with prior evidence describing the greater effectiveness of BRV in older versus younger patients 13–15 16,17 …”

“…The higher rates of SSF and SSR observed in elderly patients also agree with prior evidence describing the greater effectiveness of BRV in older versus younger patients. [13][14][15] Notably, when studies report outcomes by age class, ASMs generally are found to be more efficacious in elderly than younger patients, and differences in outcomes across the age groups can largely be attributed to differences in characteristics of participants. 16,17 BRV was discontinued by approximately 25% of the patients, and this figure substantially overlapped with the rates found in retrospective noninterventional studies 14,[18][19][20] ; the lack of efficacy was the main reason for drug withdrawal as expected according to the characteristics of the patients and study inclusion criteria.…”