Abstracts

Rationale: Levetiracetam (LEV) has been reported to be associated with non-psychotic behavioral adverse events (BAEs) such as aggression, agitation, anger, anxiety, apathy, depression, hostility and irritability. This study evaluated BAEs in patients receiving LEV who switched to brivaracetam (BRV). Methods: This was an open-label, prospective, multicenter, Phase IIIb study (NCT01653262). Patients were ≥16 years, on 2-3 AEDs including LEV 1-3g/day and experiencing BAEs (within 16 weeks of LEV initiation) warranting LEV discontinuation. After ≤1-week screening, LEV was stopped, other AEDs were not changed and BRV 200mg/day was started without titration and continued for 12 weeks. Patients who completed the study could enter a follow-up study (NCT01728077). The primary safety variable was percentage of patients with investigator-assessed clinically meaningful reduction in BAEs over treatment period. Secondary safety variables included Investigator Global Evaluation of Behavioral Side Effects (I-GEBSE), shift in maximum intensity of BAEs primarily associated with discontinuation of LEV over treatment period, complete abatement of BAEs at study end based on the investigator's assessment, freedom from BAEs over treatment period, treatment-emergent adverse events (TEAEs) and discontinuations due to TEAEs. Results: 29 patients were enrolled (51.7% male; mean age 35.8 years; mean epilepsy duration 16.2 years); 26 (89.7%) patients completed the study. At study end, 27/29 (93.1%) patients who switched to BRV had clinically meaningful reduction in investigator-rated BAEs. Marked/moderate improvements of BAEs, measured by the I-GEBSE, were reported in 20/29 (69.0%) patients; 1/29 (3.4%) reported marked worsening of BAEs. The intensity of severe BAEs associated with LEV (n=13 patients) shifted to resolved (n=8), moderate (n=3) and mild (n=2) after switching to BRV (study end); moderate BAEs with LEV (n=14) shifted to resolved (n=10), moderate (n=1) and mild (n=3) with BRV; mild BAEs with LEV (n=2) shifted to resolved (n=1) and mild (n=1) with BRV. At study end, 18/29 (62.1%) patients had complete abatement of BAEs. Three (10.3%) patients had freedom from BAEs over the treatment period. Most frequent TEAEs were consistent with the known tolerability profile of BRV except for back pain; TEAEs reported in ≥5% patients were headache (17.2%), fatigue (10.3%), back pain (10.3%), depression (6.9%), dizziness (6.9%), insomnia (6.9%), nasopharyngitis (6.9%) and tremor (6.9%). One patient (3.4%) reported a serious AE (suicide ideation; suicide attempt). Two patients (6.9%) discontinued study drug due to TEAEs. Conclusions: Findings suggest that patients who experience BAEs associated with LEV treatment may benefit from an immediate switch to BRV. However, results should be interpreted with caution owing to the small sample size and the open-label nature of the study. Further randomized, blinded studies exploring this finding would be of interest. UCB supported