WRAPPER study: Real-world effectiveness and tolerability of adjunctive perampanel for people with drug-resistant epilepsy in Hong Kong

Objective: The Prince of Wales Hospital (PWH) Real-world Analysis of People with Drug-Resistant Epilepsy (DRE) on PERampanel (WRAPPER) study assessed effectiveness and tolerability of adjunctive perampanel in people with DRE attending PWH.Methods: This was a prospective single-center real-world observational study involving 70 people with DRE between July 2016 and June 2021. A post hoc analysis after the initial study period of 16 weeks assessed outcomes for an extended period up to 52 weeks.Results: After 16 weeks, median dose of perampanel was 2 mg (IQR 24 mg). 50% responder rates were 40.0%, 41.5%, and 48.7% at 16, 26, and 52 weeks. Seizure freedom was 12.9%, 20.7%, and 25.6% at 16, 26, and 52 weeks. Monthly seizure frequency reduced from 3.0 (IQR 3.0-6.6) at baseline to 2.0 (IQR 2.0-6.0, p = 0.005) at 16 weeks; 2.0 (IQR 2.0-5.0, p = 0.01) at 26 weeks; and 2.0 (IQR 0.0-4.0, p = 0.018) at 52 weeks. Older age predicted 50% responders (OR 1.08, 95% CI 1.01-1.14, p = 0.048). At 16 weeks, 51.4% (36/70) had treatment-emergent adverse effects (TEAEs). Most common was seizure exacerbation at 35.7% (25/70) followed by fatigue at 15.7% (11/70). NPI-12 and ZBI scores indicated no increase in neuropsychiatric symptoms on perampanel.Significance: Low-dose 2-4 mg adjunctive perampanel for people with DRE conferred appreciable improvements in seizure reduction without significant neuropsychiatric adverse effects in the real-world setting at a tertiary center in Hong Kong and had better antiseizure effect with advancing age.Plain language summary: This real-world study from Hong Kong found low-dose perampanel was effective and tolerable for people with drug-resistant epilepsy. Furthermore, perampanel was also potentially more effective with advancing age.