Abstracts

Rationale: Perampanel (PER) is a first-in-class, noncompetitive AMPA antagonist and it is approved for adjunctive treatment of focal seizures, with or without secondarily generalization, and primary generalized tonic-clonic seizures in patients older than 12 years old. The aim of this study was to assess long-term effectiveness of PER as adjunctive treatment in adolescents and adults with drug-resistant epilepsy, using retention rate and relapse-free survival rate as the outcome measures.  Methods: Epileptic patients treated with PER from May 2015 to May 2018 were enrolled in this multicenter retrospective observational cohort study. Kaplan-Meier survival analysis was made to assess the time to PER failure, defined as discontinuation of PER in the whole population, and the relapse-free survival in responders. The impact of other factors including age, epileptic syndrome, duration of epilepsy, concomitant and previous treatments, titration, dosage, and neuropsychological comorbidities were evaluated using Cox Proportional Hazard Methods. Results: The series comprised 188 patients (93 females), with median age at epilepsy onset of 9 years (interquartile range [IQR]: 2-17.5 years) and a median time of disease duration prior PER of 22 years (IQR 13-35). The most frequent epileptic syndromes were: drug-resistant focal epilepsy (151 patients, 80%) and epileptic encephalopathies (28 patients, 15%). All patients received previous (median 6, IQR 4-9) and concomitant (median 2.5, IQR 2-3) treatments. The probability of remaining on PER was 63.4% at 12 months, 47% at 24 months, and 23% at 36 months. PER was discontinued by 86 (47.74%) due to inefficacy (54%), side effects (28%), or both (16%). Fourteen patients (7.4%) achieved seizure freedom, and 50 (26.6%) gained significant (= 50%) seizure reduction. The relapse-free survival in responders was 91.4% at 12 months, 59% at 24 months, and 30.2% at 36 months.The presence of intellectual disability was significantly associated with PER failure (HR 1.69, 95% CI 1.10 – 2.61, p=0.01). Conclusions: This study provides observational evidence for treatment persistence of PER in drug-resistant epilepsy using time to treatment failure, and documents a real-world progressive loss of PER efficacy over time. The presence of neuropsychological comorbidities should be kept in mind to optimize the use of PER in clinical setting. Funding: There are no known conflicts of interest associated with this abstract, and there has been no significant financial support for this work that could have influenced its outcome.