Abstracts

Rationale: Few large-scale studies have been carried out to investigate the long-term safety and efficacy of perampanel, a first-in-class antiepileptic drug (AED) developed and marketed in Japan in 2016 for use in combination with other AEDs for treatment of partial-onset seizures (with or without secondarily generalized seizures) or primary generalized tonic-clonic seizures. We carried out an interim analysis of post-marketing surveillance data to evaluate the safety and efficacy of long-term treatment with perampanel in a real-world setting.  Methods: We analyzed case report data from an ongoing prospective observational study, with a maximum 52-week follow-up period, in which Japanese epilepsy patients aged 18 years or older and receiving perampanel were enrolled. This study was conducted in accordance with Good Post-Marketing Study Practice in Japan. Results: The case report forms were collected from 641 patients who received treatment at 124 institutions across Japan between August 2016 and January 2018 (641 forms at week 24, 73 at week 52). Data from 636 patients were included in the safety analysis set (women, 46.9%; mean age, 42.2 years; mean body weight, 58.5 kg; proportion with duration of epilepsy 20 years or more, 54.9%). Regarding adjunctive therapy, 49.3% of patients received concomitant treatment with 3 or more AEDs. At 24 weeks, 71.1% of patients remained on treatment with perampanel. Data from 559 patients were included in the efficacy analysis set.Regarding safety, 30.97% of patients experienced adverse effects, including dizziness (9.43%) and somnolence (9.28%). These adverse effects occurred relatively soon after initial administration of perampanel; first onset of dizziness and somnolence occurred in 26.67% and 45.76% of patients, respectively, in the first 28 days, and in 30.00% and 33.90%, respectively, 28–56 days after administration. The incidence of falls and other disability-related adverse events caused by dizziness, balance disorder, ataxia, and muscular relaxation was 0.31%. The incidence of adverse events related to hostility and aggressiveness was 8.96% including irritability in 3.77%.Regarding efficacy, the proportion of patients who achieved =50% reduction in seizure frequency at week 24 was 68.4% in patients with partial-onset seizures with motor signs, 71.4% in those with partial-onset seizures without motor signs, 52.7% in those with complex partial-onset seizures, 73.3% in those with secondarily generalized seizures, and 60.4% in those with primary generalized tonic-clonic seizures. At week 24, 71.2% of patients were judged to have had overall symptom improvement.   Conclusions: The results of this interim analysis using real-world data from Japanese patients are similar to those of preapproval clinical trials of perampanel. Funding: This study was funded by Eisai Co., Ltd.