Authors :
Presenting Author: Patricia Penovich, MD – Minnesota Epilepsy Group PA, St Paul, MN, USA
Eric Segal, MD – Northeast Regional Epilepsy Group, Hackensack University Medical Center, Hackensack Meridian School of Medicine, Hackensack, New Jersey, USA; Michael Chez, MD – Sutter Neuroscience Institute, Roseville, California, USA; Imad Najm, MD – Cleveland Clinic, Cleveland, OH, USA; Iñigo Garamendi, MD – Cruces University Hospital, Baracaldo, Spain; Luis Morillo, MD – Hamiliton General Hospital,Hamilton Ontario, Canada; Sheri Cappucci, MD – Eisai Inc, Nutley, NJ, USA; Ricardo Sainz-Fuertes, MD – Eisai Europe Ltd; Vicente Villanueva, MD – Refractory Epilepsy Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain
Rationale:
Perampanel (PER) is a once-daily antiseizure medication (ASM) indicated for treatment of focal seizures in people with focal epilepsy and generalized tonic-clonic seizures in people with idiopathic generalized epilepsy. The PERMIT Extension study is the largest pooled analysis of PER clinical practice data conducted to date. It demonstrated that PER is effective and generally well tolerated when used to treat people with focal or generalized epilepsy in everyday clinical practice. This analysis investigated the effectiveness and safety/tolerability of PER according to the most frequently used concomitant ASMs in PERMIT Extension.
Methods:
PERMIT Extension was a pooled analysis of data from PERMIT (a global pooled analysis of 44 real-world studies of patients with focal and generalized epilepsy treated with PER) and PROVE (a Phase IV, retrospective, noninterventional study of PER when used during routine clinical care in the USA). The current analysis assessed the effectiveness and safety/tolerability of PER when used in combination with the five most frequently used concomitant ASM treatments in people with epilepsy (PWE) with only focal or generalized seizures. Effectiveness assessments included 50% responder rate (≥50% seizure frequency reduction) and seizure freedom rate (no seizures since at least the prior visit) at the last visit (last observation carried forward). Safety/tolerability was assessed by evaluating the incidence of adverse events (AEs).
Results:
Of the 6822 PWE included in PERMIT Extension (mean time under PER treatment 10.54 months), the type(s) of concomitant ASMs used at baseline was known for 5144 PWE (50.7% female; mean age, 37.8 years; mean number of concomitant ASMs at baseline, 2.3) who had only focal (n= 4347) or generalized (n=797) seizures. Of these, 3708 were assessed for effectiveness (focal, n=3230; generalized, n=478) and 4754 for tolerability (focal, n=3980; generalized, n=774). When PER was initiated, the proportions of PWE treated with 1, 2, 3 or >3 concomitant ASMs were 25.0%, 37.7%, 26.2% and 11.0%, respectively. The five most frequently used ASM treatments at baseline were levetiracetam (5.7%), lamotrigine (3.3%), lacosamide+levetiracetam (3.0%), valproate (2.6%), and carbamazepine (2.5%) in PWE with focal seizures, and levetiracetam (14.1%), valproate (7.2%), levetiracetam+valproate (5.4%), lamotrigine (5.0%), and topiramate (2.8%) in PWE with generalized seizures. The effectiveness and safety/tolerability of PER in PWE receiving these ASM treatments at baseline are summarized in Figures 1 and 2, respectively.
Conclusions:
PER was effective and generally well tolerated in PWE with focal and generalized seizures. The effectiveness and safety/tolerability of PER varied considerably depending on which concomitant ASMs were used, illustrating the importance of considering the benefit‒risk of individual combinations of ASMs when making treatment decisions in clinical practice.
Funding: Supported by Eisai