Effect of early tolerability and co-medication on long-term perampanel treatment outcomes in real-world settings

Perampanel is a widely administered anti-seizure medication (ASM), suitable for epilepsy polytherapy, including drug-resistant epilepsy. However, real-world data on long-term retention, responder and seizure-freedom rates are limited. This study aims to evaluate 24-month retention, responder and seizure freedom rates of perampanel treatment, focusing on adverse events and concomitant ASMs.

This retrospective observational study included patients (≥ 18 years) with epilepsy, who initiated perampanel treatment between December 2018 and October 2023 at Asan Medical Center. The retention, responder (≥ 50% seizure reduction), seizure-freedom rates and adverse events were assessed at 3, 6, 12 and 24 months.

Among 139 patients (mean age 44.7 ± 15.0 years; 55.4% male), the 24-month retention rate was 59.7%. Most discontinuations occurred within the first 3 months, 83.9% due to adverse events, with dizziness being the most common in the cohort (47.2%) and among discontinued patients (33.9%). Retention, responder and seizure-freedom rates were lower in patients with adverse events. Patients receiving enzyme-inducing anti-seizure medications (EIASMs), particularly oxcarbazepine and carbamazepine, had lower retention, responder and seizure-freedom rate, while those receiving levetiracetam or lamotrigine demonstrated higher retention and seizure-freedom rates, with fewer adverse events.

In this real-world study, the first 3 months after perampanel initiation represent a critical period for optimising retention and seizure control through adverse event management. Concomitant use of EIASM, may be associated with difference in efficacy. Early monitoring of adverse events and appropriate consideration of concomitant ASMs may optimise long-term perampanel treatment outcomes.