Efficacy and tolerability of adjunctive brivaracetam in patients with prior antiepileptic drug exposure: A post-hoc study

Abstract

Brivaracetam (BRV), a selective, high-affinity ligand for synaptic vesicle protein 2A, is a new antiepileptic drug (AED) for adjunctive treatment of focal (partial-onset) seizures in adults with epilepsy. This post-hoc analysis was conducted to explore the efficacy of adjunctive BRV in patients with prior levetiracetam (LEV) exposure and whether changes in efficacy were related to the similar mechanism of action of these two drugs. Data were pooled from three Phase III studies (NCT00490035; NCT00464269; NCT01261325) of adults with focal seizures taking 1-2 AEDs who received placebo or BRV 50-200mg/day without titration over a 12-week treatment period. Patients taking concomitant LEV at enrollment were excluded from this analysis. Patients were categorized by their status of prior exposure to LEV, carbamazepine (CBZ), topiramate (TPM), or lamotrigine (LTG), to investigate any consistent trend towards reduced response in AED-exposed subgroups compared to AED-naïve subgroups, regardless of the mechanism of action. Study completion rates, percent reduction from baseline in focal seizure frequency over placebo, ≥50% responder rates, and tolerability were evaluated for each subgroup. A total of 1160 patients were investigated. Study completion rates were similar in the AED-exposed subgroups and AED-naïve subgroups. In subgroups with (531 patients) or without (629 patients) prior LEV exposure, ≥50% responder rates for each dose of BRV compared with placebo were generally higher among the LEV-naïve subgroups than the previously LEV-exposed subgroups. LEV-exposed subgroups receiving BRV doses ≥50mg/day showed greater ≥50% responder rates than those receiving placebo. Similar results were observed for CBZ, TPM, and LTG. Previous treatment failure with commonly prescribed AEDs (LEV, CBZ, TPM, or LTG) is associated with a reduced response to BRV irrespective of the mechanism of action. Hence, this post-hoc analysis indicates that previous treatment failure with LEV does not preclude the use of BRV in patients with epilepsy.

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

“…In the three phase III studies on BRV, concomitant LEV use was either limited to 20%7 9 of the patient population or patients who had taken LEV within the last 90 days were excluded 8. However, these studies point to an effect of BRV even in patients who have previously taken LEV, possibly with a slightly lower responder rate 7–9 11 12. Our data show that BRV is significantly less effective in patients who have been treated with LEV, but BRV still leads to seizure reduction in 42% of these patients and there is no significant difference in the proportion of patients who become seizure free compared with patients who are LEV naïve.…”

A review of the pharmacology and clinical efficacy of brivaracetam

“…In this analysis, evaluation of patients receiving BRV 50–200 mg/day (n=1,160) by prior exposure to LEV and three other commonly used AEDs – carbamazepine, topiramate, and lamotrigine – showed that patients previously treated by any of these four AEDs all had reduced response to BRV compared with patients not previously treated by the same AEDs. 100 A total of 578 patients had prior exposure to LEV, 424 to carbamazepine, 428 to topiramate, and 349 to lamotrigine. The proportion of patients who had previously had more than five AEDs fail was higher among previously LEV-, carbamazepine-, topiramate-, and lamotrigine-exposed subgroups (61%–69%) than among subgroups never exposed to those AEDs (13%–17%).…”

Economic Value of Adjunctive Brivaracetam Treatment Strategy for Focal Onset Seizures in Finland

“…Brivaracetam proved its efficacy and rapid onset of therapeutic dose in the treatment of focal onset seizures [25][26][27][28] while also preserving good tolerance [22][23][24][25][26][27][28]. Even previous treatment failure with levetiracetam does not preclude the use of brivaracetam [30].…”

“…Brivaracetam is a well-tolerated [22][23][24][25][26][27][28] and efficacious [25][26][27][28][29] ''next-generation racetam'' that requires no uptitration to achieve the therapeutic dose range. Furthermore, previous treatment failures with other AEDs or racetams (e.g., levetiracetam) do not preclude the use of brivaracetam [30].…”