Effectiveness of perampanel as only concomitant antiseizure medication for highly active epilepsy: insight from a real-world, multicenter retrospective study

Introduction: Managing patients with highly frequent seizures poses significant challenges for clinicians due to their high resistance to therapy. This study aims to evaluate the 12-month efficacy, safety, and tolerability of PER as the sole add-on therapy for patients with highly active epilepsy in a real-world setting. Methods: Data from the previous Italian retrospective, observational, multicenter "PERampanel as Only Concomitant Antiseizure Medication" (PEROC) study were analyzed, categorizing patients by baseline seizure frequency into three groups: < 5, 5-20, and > 20 seizures/month. Retention, responder (≥ 50% seizure reduction) rates, seizure-free rates and adverse events (AEs) were analyzed. Sub-analyses examined early (≤ 1 previous ASM) vs. late (> 2 previous ASMs) add-on groups. Results: The sample included 485 patients with focal and generalized epilepsy: 354 with < 5 seizures/month, 79 with 5-20, and 52 with > 20 seizures/month. Retention rates at 12 months were 75.1%, 68%, and 58.1.7%, respectively. Perampanel significantly reduced seizure frequency in all groups, with responder rates of 71.2%, 61.8%, and 63.2% at the 12-month follow-up. Patients with more frequent seizures (> 20 and 5-20 seizures/month) had lower seizure-free rates (15.8% and 23.5%) compared to those with < 5 seizures/month (49.5%, p = 0.001). AEs, mainly dizziness and irritability occurred in 30% of patients, without significant differences between groups (p = 0.092). Conclusions: PER, as the sole adjunctive therapy, demonstrated good effectiveness and tolerability in a real-world setting, even for patients with highly active epilepsy. These findings suggest PER as a valuable early treatment option to improve seizure control and quality of life in this challenging population.