Abstracts

Rationale: Brivaracetam (BRV) is approved in the US for treatment of focal epilepsy in doses up to 200 mg/day. Early pharmacokinetic studies showed good tolerability of single BRV doses up to 1000 mg and of repeated doses of up to 800 mg/day. The purpose of this study is to audit charts of patients treated with higher doses of BRV higher than 200 mg/day to ascertain efficacy and safety of BRV doses of > 200 mg/day add-on treatment in adults with refractory focal epilepsy. Methods: This is a single center chart review study. All charts of patients treated with > 200 mg/day BRV were reviewed. All patients had kept prospective seizure diaries for > 6 months before BRV treatment initiation and during treatment with BRV. Patients were initially titrated to 200 mg/day. The dose was increased to > 200 mg/day if they had not responded or responded partially without side effects at doses up to 200 mg/day. Patients were titrated up to seizure freedom, or side effects whichever came first. Titration rate was individualized by clinical judgment. Treatment lasted 12 weeks at > 200 mg/day dose. Primary efficacy outcome measure was seizure count/28 days. Primary efficacy outcomes were 100% and >75% seizure reduction. Safety outcome measures were TEAEs, treatment discontinuation due to TEAEs and SAEs. Results: Fifteen patients with refractory epilepsy were treated with BRV > 200 mg/day (8M, mean age 47.1 years, range 36-68, epilepsy duration > 20 years in 13/15). All patients had failed > 3 prior AEDS, 12/15 (80%) patients had failed > 5 prior AEDS. Doses ranged from 250 mg/day (n=1) to 700 mg/day (n=2). Median dose was 500 mg/day. 13 patients were treated with > 300 mg/day. All 15 patients completed the 12 weeks’ treatment at > 200 mg/day. 3 patients had > 50% seizure frequency reduction with dose increase above 200 mg/day compared with BRV dose up to 200 mg/day. No patients had > 75 % seizure frequency reduction. Main side effects were somnolence and dizziness. Most TEAEs were mild to moderate in severity and resolved with dose reduction. There were no SAEs. No patient stopped the medication because of side effects, although side effects resulted in dose reduction in 5/15 patients. Commonest TEAEs were somnolence/fatigue and dizziness/ataxia. Irritability occurred in 1 patient. Conclusions: Adjunctive brivaracetam treatment with doses > 200 mg/day confers little benefit additional to BRV treatment with 200 mg/day. Funding: No funding