Effectiveness and safety of perampanel monotherapy for focal and generalized tonic-clonic seizures: Experience from a national multicenter registry
Rafael Toledano Delgado 1 2 , Irene García-Morales 2 3 , Beatriz Parejo-Carbonell 3 , Adolfo Jiménez-Huete 4 , David Herrera-Ramirez 2 , Ayoze González-Hernández 5 , Fernando Ayuga Loro 6 , Estevo Santamarina 7 , Manuel Toledo 7 , Joaquín Ojeda 8 , Juan José Poza 9 , Albert Molins 10 , Pau Giner 11 , José Carlos Estévez María 12 , María Dolores Castro-Vilanova 13 , Jorge Zurita 14 , Rosa Ana Saiz-Diaz 15 , Asier Gómez-Ibañez 16 , Juan Rodriguez-Uranga 17 , Antonio Gil-Nagel 2 , Dulce Campos 18 , Álvaro Sánchez-Larsen 19 , Maria José Aguilar-Amat Prior 20 , José Angel Mauri Llerda 21 , Nuria Huertas González 22 , Nuria García-Barragán 1
Objective: To assess the effectiveness and tolerability of perampanel (PER) monotherapy in routine clinical practice for the treatment of focal onset and generalized tonic-clonic seizures (GTCS).
Methods: This multicenter, retrospective, observational study was conducted in patients aged ≥12 years treated with PER as primary monotherapy or converted to PER monotherapy by progressive reduction of background antiepileptic drugs. Outcomes included retention, responder, and seizure-free rate after 3, 6, and 12 months and tolerability throughout the follow-up.
Results: A total of 98 patients (mean age = 49.6 ± 21.7 years, 51% female) with focal seizures and/or GTCS were treated with PER monotherapy for a median exposure of 14 months (range = 1-57) with a median dose of 4 mg (range = 2-10). The retention rates at 3, 6, and 12 months and last follow-up were 93.8%, 89.3%, 80.9%, and 71.4%, respectively. The retention rates according to the type of monotherapy (primary vs conversion) did not differ (log-rank P value = .57). Among the 98 patients, 61.2% patients had seizures throughout the baseline period, with a median seizure frequency of 0.6 seizures per month (range = 0.3-26). Responder rates at 3, 6, and 12 months were 79.6%, 70.1%, and 52.8%, respectively, and seizure freedom rates at the same points were 62.7%, 56.1%, and 41.5%. Regarding the 33 patients who had GTCS in the baseline period, 87.8% were seizure-free at 3 months, 78.1% at 6 months, and 55.1% at 12 months. Over the entire follow-up, PER monotherapy was generally well tolerated, and only 16% of patients discontinued PER due to adverse events (AEs). Female patients were found to be at a higher risk of psychiatric AEs (female vs male odds ratio = 2.85, 95% confidence interval = 1-8.33, P = .046).
Significance: PER demonstrated good effectiveness and a good safety profile when used as primary therapy or conversion to monotherapy at relatively low doses, in a clinical setting with patients with focal seizures and GTCS.