An open-label, prospective, exploratory study of patients with epilepsy switching from levetiracetam to brivaracetam

Abstract

We evaluated nonpsychotic behavioral adverse events (BAEs) in patients receiving levetiracetam (LEV) who switched to brivaracetam (BRV). Patients ≥16 years of age, receiving 2-3 antiepileptic drugs (AEDs), including LEV 1-3g/day, and experiencing BAEs within 16 weeks of LEV treatment initiation, enrolled in an open-label Phase 3b study (NCT01653262) comprising a ≤1-week screening period, an immediate switch from LEV to BRV 200mg/day (without titration), and a 12-week treatment period. The percentages of patients with investigator-assessed clinically meaningful reduction in BAEs, shift in maximum BAE intensity, and change in health-related quality of life (HRQoL) (Patient-Weighted Quality of Life in Epilepsy Inventory-Form 31 [QOLIE-31-P]) were assessed. Of 29 patients enrolled, 26 (89.7%) completed the study. At the end of the treatment period, 27/29 (93.1%) patients switched to BRV had clinically meaningful reductions in BAEs. Physicians reported a reduction in the maximum intensity of primary BAEs in 27/29 (93.1%) patients. Mean change from baseline to Week 12 in QOLIE-31-P total score was 12.1, indicating improved HRQoL. During the treatment period, 23/29 (79.3%) patients reported treatment-emergent adverse events (TEAEs). One patient reported a serious TEAE (suicidal ideation and suicide attempt). Two patients discontinued BRV because of TEAEs. Findings from this small study suggest that patients experiencing BAEs associated with LEV may benefit from switching to BRV.

Postmarketing experience with brivaracetam in the treatment of epilepsies: A multicenter cohort study from Germany

“…Patients never previously exposed to LEV seem to have an intermediate risk of developing BAE in 15.3% (4/26) of the cases. The amelioration of BAE due to switch from LEV to BRV has already been studied in an open‐label, prospective, exploratory study . Patients underwent an immediate switch from LEV 1–3 g/day to BRV 200 mg/day without titration.…”

“…BRV showed promising results in clinical trials and had low discontinuation rates . According to a smaller scope study in 29 patients, an immediate switch from LEV to BRV seems feasible without titration and might alleviate LEV‐induced behavioral adverse events (BAEs) . The main treatment‐emergent adverse events (TEAEs) observed during the regulatory trials were somnolence, dizziness and psychobehavioral symptoms …”

Synaptic Vesicle Glycoprotein 2A Ligands in the Treatment of Epilepsy and Beyond

“…The most serious adverse effects of levetiracetam are behavioral in nature and are more common in children and in adult epilepsy patients with a prior history of behavioral problems and psychiatric disease [110]. The more selective SV2A mechanism of brivaracetam versus levetiracetam triggered UCB to perform a small, open-label study to assess if brivaracetam may be associated with fewer behavioral adverse effects [111]. This study showed that epilepsy patients experiencing behavioral adverse effects associated with levetiracetam benefited from switching to brivaracetam.…”

Outcomes in three cases after brivaracetam treatment during pregnancy

“…It may be dosed at 25‐100 mg twice daily. It is an attractive alternative to LEV for patients experiencing psychiatric side effects …”