Abstracts

Rationale: Brivaracetam (BRV), a selective, high-affinity ligand for synaptic vesicle protein 2A, is a new antiepileptic drug (AED) approved for adjunctive treatment of focal (partial-onset) seizures in adults (≥16 years). Pooled long-term data for adjunctive treatment of focal seizures have been reported with a cut-off date of January 17, 2014.1 This analysis reports updated safety and tolerability data up to a cutoff of August 31, 2016. Methods: Data were pooled from two Phase II (NCT00175929, NCT00175825), six Phase III (NCT00490035, NCT00464269, NCT00504881, NCT01405508, NCT01261325, NCT01653262), and associated long-term follow-up (LTFU) studies (NCT00175916, NCT00150800, NCT01728077, NCT01339559). Adults with epilepsy received BRV 5–200 mg/day. Safety/tolerability assessments were done at protocol-specified time points. Patients were asked at study visits if they had experienced adverse events (AEs) and could spontaneously report AEs at any time. Results: Of 2437 patients (97.2% with focal seizures, 2.8% with other seizure types) who received BRV, treatment is ongoing in 578 (23.7%). In addition, 216 (8.9%) completed LTFU, 1581 (64.9%) discontinued treatment in core or LTFU studies, and 62 (2.5%) completed core studies but did not enter LTFU. At baseline, mean (SD) age was 37.1 (12.6) years; 50.5% were male. Total exposure was 7878.9 patient-years; 1650, 1355, 579, 508, 472, 326, 93, and 87 patients were exposed to BRV for at least 12, 24, 60, 72, 84, 96, 108, and 120 months, respectively. Six patients were exposed to BRV for >11 years. Most common concomitant AEDs (≥20%) were carbamazepine (42.2%), lamotrigine (28.1%), and valproate (24.6%). Overall, 89.2% patients reported treatment-emergent adverse events (TEAEs) (57.0% drug related). There was no evidence to suggest that TEAE incidence increased with higher modal dose (Table). The most common TEAEs (≥10% overall) were headache (22.5%), dizziness (19.4%), somnolence (16.1%), nasopharyngitis (14.3%), fatigue (12.4%), and convulsion (12.0%). Serious TEAEs (SAEs) were reported in 22.1% of patients (4.6% drug related), most commonly (≥0.5%) convulsion (2.9%), status epilepticus (1.1%), epilepsy (0.8%), pneumonia (0.7%), suicidal attempt (0.7%), suicidal ideation (0.6%), fall (0.5%), and pregnancy (0.5%). Overall, 15.5% of patients discontinued BRV due to TEAEs; most frequently (≥0.5%) convulsion (1.6%), pregnancy (1.2%), depression (0.9%), dizziness (0.9%), fatigue (0.7%), somnolence (0.7%), suicidal ideation (0.7%), irritability (0.6%), and suicide attempt (0.6%). There were 40 (1.6%) deaths. Vital signs, electrocardiograms, and laboratory assessments did not reveal any clinical concerns. Conclusions: Pooled long-term data show that treatment with adjunctive BRV for up to 11 years was generally well tolerated. The long-term safety profile of adjunctive BRV was consistent with that reported previously for up to 8.5 years’ treatment.1 1Toledo M et al. Epilepsia 2016;57:1139−1151 Funding: Studies supported by UCB Pharma