Authors :
First Author: Norman Delanty, MD – Department of Neurology, Beaumont Hospital, Dublin, Ireland
Presenting Author: Sheri Cappucci, – Eisai
Rajiv Mohanraj, MD – Greater Manchester Neurosciences Centre, Salford Royal Hospital, Salford, UK; Rohit Shankar, MD – Peninsula School of Medicine, Plymouth, UK; Tim Wehner, MD – UCL Institute of Neurology, Queen Square, London, UK; Linda Stephen, MD – Epilepsy Unit, West Glasgow Ambulatory Care Hospital, Glasgow, Scotland, UK; Paola De Liso, MD – Bambino Gesù Children's Hospital, IRCCS, Rome, Italy; Wendyl D’Souza, MD – Department of Medicine, St Vincent's Hospital Melbourne, The University of Melbourne, Victoria, Australia; 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:
A genetic contribution to etiology is estimated to be present in up to forty percent of people with epilepsy (PWE). The International League Against Epilepsy considers genetic epilepsies to be those resulting directly from a known or presumed genetic mutation in which seizures are a core symptom of the disorder. Perampanel (PER) is a once-daily antiseizure medication indicated for treatment of focal seizures in people with focal epilepsy and generalized tonic-clonic seizures in people with idiopathic generalized epilepsy (IGE). 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 in PWE with a genetic etiology who were included 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 PWE with a genetic etiology (as defined by participating physicians). Retention was assessed after 12 months of PER treatment; effectiveness was assessed at 12 months and the last visit (last observation carried forward). Effectiveness assessments included responder rate (≥50% seizure frequency reduction) and seizure freedom rate (no seizures since at least the prior visit). Safety/tolerability was assessed by evaluating the incidence of adverse events (AEs).
Results:
Etiology was known for 5582 of the 6822 PWE included in PERMIT Extension, of whom 1012 had a genetic etiology (54.5% female; mean age, 30.0 years; mean duration of epilepsy, 17.5 years). These PWE had a range of genetic etiologies, the most common ( >5 PWE) being IGE (n=589), tuberous sclerosis (n=11) and Dravet syndrome (n=8) (Table 1). Retention, responder and seizure freedom rates at 12 months are shown in Figure 1. At the last visit, responder rates for the total population with genetic etiology and the subgroups with IGE, tuberous sclerosis and Dravet syndrome were 68.3%, 84.4%, 57.1% and 71.4%, respectively, and the corresponding seizure freedom rates were 46.5%, 64.6%, 22.2% and 28.6%, respectively. The incidences of AEs in the total population with genetic etiology and the subgroups with IGE, tuberous sclerosis and Dravet syndrome were 46.5%, 48.8%, 27.3% and 62.5%, respectively, and the corresponding rates of discontinuation due to AEs over 12 months were 16.4%, 17.1%, 12.5% and 25.0%, respectively.
Conclusions:
PER was effective and generally well tolerated when used to treat PWE with a range of genetic etiologies.
Funding: Supported by Eisai