Abstracts

Rationale: Perampanel is a once-daily oral anti-seizure drug (ASD) for partial-onset seizures and primary generalized tonic-clonic seizures. There are limited data on real-world use of perampanel as an ASD in the United States. PROVE (Study 506; NCT03208660) is a retrospective, multicenter, non-interventional Phase IV study assessing retention rate, safety, and dosing experience of perampanel administered to patients with epilepsy during routine clinical care. Here, we report the results of retention rates by enzyme-inducing anti-seizure drugs (EIASDs) and non-EIASDs. Methods: Data were obtained from medical records of patients who initiated perampanel treatment after January 1, 2014. Follow-up was completed on March 15, 2019. Patients were analyzed by those receiving EIASDs or non-EIASDs, and endpoints included retention rate, response rate, dosing experience, and monitoring of treatment-emergent adverse events (TEAEs). Results: In the Safety Analysis Set (N=1693), 342 patients received EIASDs and 1351 received non-EIASDs. Mean (standard deviation), modal, and maximum doses were 6.2 (4.2) and 7.4 (4.3) mg/day (EIASDs), and 5.8 (3.0) and 6.4 (3.1) mg/day (non-EIASDs), respectively. The most common modal daily perampanel doses were 2 mg (EIASDs: n=42 [12.3%]; non-EIASDs: n=192 [14.2%]), 4 mg (EIASDs, n=64 [18.7%]; non-EIASDs: n=258 [19.1%]), 6 mg (EIASDs: n=54 [15.8%]; non-EIASDs: n=235 [17.4%]), and 8 mg (EIASDs: n=51 [14.9%]; non-EIASDs: n=211 [15.6%]). Retention rates were similar for both groups across 2 years (Figure 1). The 50% responder and seizure-freedom rates were generally similar for both groups; however, at 22 to 24 months more patients were responders in the non-EIASD vs. the EIASD group (Figure 2A, 2B). An improvement, no change, or worsening of seizures was reported in 50.4% (n=141), 36.8% (n=103), and 12.9% (n=36) of patients with EIASDs, and 52.0% (n=585), 35.8% (n=403), and 12.3% (n=138) of patients with non-EIASDs, respectively. TEAEs occurred in 141 (41.2%) patients with EIASDs and 530 (39.2%) with non-EIASDs. The most common was dizziness (EIASDs: n=26 [7.6%]; non-EIASDs: n=97 [7.2%]). TEAEs leading to dose withdrawal occurred in 75 (21.9%) patients with EIASDs and 307 (22.7%) with non-EIASDs. Serious TEAEs occurred in 15 (4.4%) patients with EIASDs and 53 (3.9%) patients with non-EIASDs. Conclusions: The results from Study 506 suggest that daily oral doses of adjunctive perampanel were generally well tolerated, with favorable retention rates for up to 2 years in patients receiving EIASDs and non-EIASDs. At 18 months, 50% responder rates and seizure-freedom rates were similar in the EIASD and non-EIASD cohorts. Funding: Eisai Inc.