Perampanel Monotherapy for the Treatment of Epilepsy: Evidence From a Clinical Trial (Study 342) and Real-World Use (Studies 504 and 506)

초록

Objective: Assess efficacy/safety of perampanel monotherapy in patients with epilepsy using data from clinical and real-world studies. Background: In the US and Japan, perampanel is approved for partial-onset seizures (POS; adjunctive/monotherapy) in patients aged ≥4 years and primary generalized tonic-clonic seizures (adjunctive) in patients aged ≥12 years. Design/Methods: Patients with epilepsy were included in Studies 504 (if prescribed perampanel monotherapy) and 506 (if initiating perampanel after January 1, 2014); patients received perampanel as primary/secondary monotherapy. Study 342 recruited untreated patients aged 12–74 years with POS, with/without secondarily generalized seizures (SGS); patients received perampanel 4 mg/day (maximum: 8 mg/day). Endpoints: retention rate (Studies 504/506, primary); seizure-freedom rate (Study 342, primary; Studies 504/506, secondary); treatment-emergent adverse events (TEAEs). Results: In Study 504, 60 patients received perampanel monotherapy. Retention rates at 12 and 24 months were 55.6% (n=15/27) and 60.0% (n=3/5), respectively. Mean (standard deviation [SD]) maximum dose: 7.3 (2.8) mg/day. Seizure-freedom rate for ≥3 months was 55.0% (n=22/40). In Study 506, 47 patients received perampanel monotherapy. Retention rates at 12 and 24 months were 48.7% (n=19/39) and 45.5% (n=10/22), respectively. Mean (SD) maximum dose: 7.2 (2.7) mg/day. Seizure-freedom rate was 100.0% (n=2/2) at Months 22–24. Most patients in Studies 504 and 506 had refractory epilepsy. In Study 342, 89 patients received ≥1 perampanel dose. Mean (SD) maximum dose: 4.9 (1.7) mg/day. Most patients with ≥1 post-dose efficacy measurement in the 4-mg Maintenance Period (n=73) achieved seizure freedom (4 mg/day: 63.0%; 4 or 8 mg/day: 74.0%). TEAEs occurred in 22/60 (36.7%) and 17/47 (36.2%) patients in Studies 504 and 506, respectively, and 57/89 (64.0%; 4 mg/day) and 67/89 (75.3%; 4 or 8 mg/day) patients in Study 342. Most common TEAE was dizziness. Conclusions: These data support perampanel monotherapy as treatment for POS, with/without SGS, and refractory epilepsy.