Adjunctive brivaracetam - A prospective audit of outcomes from an epilepsy clinic.

Objective: Brivaracetam (BRV), is licensed in Europe as adjunctive treatment, and in the United States of America as adjunctive and monotherapy for focal seizures with or without secondary generalization in adults, adolescents, and children ≥4 years. As BRV becomes available globally, this prospective audit was undertaken to gain an understanding of how best to use the anti-seizure medication (ASM) in the everyday clinical setting.

Methods: Brivaracetam was started by patients ≥16 years with difficult-to-control epilepsy at Glasgow epilepsy clinics following a 12-week baseline on stable ASM doses. Target dosing was 200 mg/day. Review occurred every 12-16 weeks until 1 of 4 end-points occurred: seizure freedom for ≥6 months on a given BRV dose; ≥50% (responder) or <50% (marginal benefit) seizure reduction over 6 months compared with baseline on the highest tolerated BRV dose; withdrawal of BRV due to lack of efficacy, adverse effects, or both.

Results: An end-point has been reached by 108 patients (38 men, 70 women; median age 45 years), 88 with focal-onset seizures and 20 with genetic generalized epilepsies (GGEs). Of these, 71 (65.7%) have benefitted from BRV, including 23 (21.3%) who have been seizure free for ≥6 months on a median BRV dose of 100 mg/day (range 25-200 mg/day). A further 18 (16.7%) were classified as responders and 30 (27.8%) showed marginal benefit. Brivaracetam benefitted 16 (80.0%) patients with GGEs, 5 becoming seizure free. Generalized tonic-clonic seizures, absences, and myoclonic seizures were completely controlled in 4 (25%) patients with juvenile myoclonic epilepsy. Brivaracetam monotherapy was established in 12 patients, 3 of whom had GGEs. Levetiracetam (LEV) had previously been prescribed in 53 patients who had discontinued the ASM due to lack of efficacy, side effects, or both. Adjunctive BRV benefitted 34 (64.2%) of these patients. Brivaracetam was withdrawn in 37 (34.3%) patients, (23 side effects, 4 lack of efficacy, 10 both). Sedation was the commonest side effect leading to BRV withdrawal (n = 14; 13.0%). Psychiatric side effects resulted in BRV discontinuation in 9 (8.3%) patients.

Significance: Brivaracetam has efficacy for a range of seizure types and syndromes in a wide range of doses. The ASM can produce positive outcomes in patients who have failed LEV. Post-marketing studies remain a useful tool to evaluate the efficacy and tolerability of novel ASMs in everyday clinical practice.