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

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

Efficacy, safety, and tolerability of adjunctive brivaracetam for secondarily generalized tonic-clonic seizures: Pooled results from three Phase III studies

AbstractPurposeSecondarily generalized tonic-clonic seizures (SGTCS) are among the most devastating types of seizures, contributing to increased morbidity and mortality. Brivaracetam (BRV), a selective, high-affinity ligand for synaptic vesicle 2A (SV2A), has been shown to be useful for the adjunctive treatment of focal seizures. We sought to determine its specific efficacy in treating SGTCS.MethodsData were pooled from three Phase III studies (NCT00490035; NCT00464269; NCT01261325) of adults with focal seizures taking 1⿿2 antiepileptic drugs (AEDs) who received placebo or BRV 50⿿200mg/day without titration over a 12-week treatment period. We report efficacy and safety/tolerability data for the BRV therapeutic dose range (50⿿200 mg/day) in patients with focal seizures including baseline SGTCS.ResultsPatients (efficacy population, N=409) had been diagnosed with epilepsy for a mean±standard deviation duration of 22.2±13.1years. Baseline median SGTCS frequency was 3.0 per 28days. The majority (293, 71.6%) had failed ⿥2 AEDs prior to study enrollment. The median percent reduction from baseline in SGTCS frequency/28days was: placebo, 33.3%; BRV 50mg/day, 66.6% (p<0.001); BRV 100mg/day, 61.2% (p=0.002); and BRV 200mg/day, 82.1% (p<0.001). The ⿥50% responder rate for SGTCS was: placebo, 33.0%; BRV 50mg/day, 61.3% (p=0.003); BRV 100mg/day, 55.0% (p<0.001); and BRV 200mg/day, 64.0% (p<0.001). Freedom from SGTCS was achieved by: placebo, 14.8%; BRV 50mg/day, 22.6%; BRV 100mg/day, 31.0%; and BRV 200mg/day, 36.0% of patients. Time to first SGTCS during the treatment period was longer in patients receiving BRV than placebo (26days vs 8days, hazard ratio 0.55, p<0.001). In the SGTCS safety population (N=487), treatment-emergent adverse events (TEAEs) were reported by 60.6% of patients receiving placebo vs 65.0% of patients receiving BRV ⿥50mg/day. Serious TEAEs were reported by 3.1% placebo vs 3.9% BRV ⿥50mg/day. Discontinuations due to TEAEs were 3.9% placebo vs 6.3% BRV ⿥50mg/day.ConclusionsIn patients with drug-resistant focal seizures, adjunctive BRV is effective in reducing the frequency of SGTCS. Almost one-third (30.4%) of patients were rendered completely free of SGTCS during the 12-week treatment period when taking BRV ⿥50mg/day. BRV was well tolerated, with a TEAE profile consistent with that of the overall study population