title: 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.
authors.affiliation: Jefferson Comprehensive Epilepsy Center, Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA. Electronic address: aliasadipooya@yahoo.com.
authors.forename: Ali A
authors.initials: AA
authors.lastname: Asadi-Pooya
authors.affiliation: Jefferson Comprehensive Epilepsy Center, Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Sperling
authors.affiliation: Banner University Medical Center, Phoenix, AZ, USA.
authors.forename: Steve
authors.initials: S
authors.lastname: Chung
authors.affiliation: Mid-Atlantic Epilepsy and Sleep Center, Bethesda, MD, USA.
authors.forename: Pavel
authors.initials: P
authors.lastname: Klein
authors.affiliation: UCB Pharma, Smyrna, GA, USA.
authors.forename: Anyzeila
authors.initials: A
authors.lastname: Diaz
authors.affiliation: UCB Pharma, Raleigh, NC, USA.
authors.forename: Sami
authors.initials: S
authors.lastname: Elmoufti
authors.affiliation: UCB Pharma, Raleigh, NC, USA.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Schiemann
authors.affiliation: UCB Pharma, Raleigh, NC, USA.
authors.forename: John
authors.initials: J
authors.lastname: Whitesides
mesh_terms: D000927:Anticonvulsants / Q000008:administration & dosage*; D017326:Clinical Trials, Phase III as Topic / Q000379:methods*; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D011760:Pyrrolidinones / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; D011760:Pyrrolidinones; C482793:brivaracetam
keywords: Antiepileptic drug; Brivaracetam; Efficacy; Failure; Tolerability