The real-world effectiveness and safety of perampanel in Europe: A scoping review.

In order to characterize the real-world effectiveness and safety of perampanel during clinical use in Europe, we conducted a structured literature search and scoping review of real-world studies conducted in Europe in adolescents (aged ≥ 12 years) or adults who were prescribed perampanel for focal epilepsy or primary generalized tonic-clonic seizures in the context of idiopathic generalized epilepsy, published between January 2016 and July 2021. We identified 29 relevant studies (20 retrospective and 9 prospective) in 3608 patients; median study duration was 12 months. Most patients (76.1%) were receiving two or more antiseizure drugs (ASDs) when perampanel was initiated. The maintenance perampanel dose ranged from 2 to 16 mg/day (most commonly 6 mg/day). Retention rate at 12 months ranged from 46% to 90.5% (median 71.1%). The proportion of patients who were free of seizures during perampanel ranged from 1.8% to 84.6%, but were consistently below 20% in studies where patients had received an average of ≥5 prior ASDs and above 20% where patients had received an average of <5 prior ASDs. The proportion of patients who achieved ≥50% reduction in seizures during perampanel ranged from 20.0% to 85.7%. Across all studies, the incidence of adverse events (AEs) ranged from 18.2% to 67.4% (median 37.1%) and discontinuation due to AEs from 6.2% to 56% (median 12.5%). Discontinuation rates tended to be higher in UK studies than in studies from Italy or Spain. The most commonly reported individual AEs were dizziness/vertigo (median incidence 13.7%), somnolence (median 11.9%), aggression (median 9.8%), irritability (median 9.1%), and cognitive deficits (median 7.0%). There was no relationship between the overall rate of AEs and perampanel dose, perampanel plasma levels, or number of concomitant medications. Our global overview of European observational studies with perampanel provides evidence that this agent is effective and safe in clinical practice in a range of countries, patients, and settings.