Authors :
First Author: Anna Gentile, PhD Scientist – Eisai S.r.l., Milan, Italy
Presenting Author: Leock Y Ngo, PhD – Pharma Industry
Presenting Author: Leock Y Ngo, PhD – Pharma Industry
Presenting Author: Leock Y Ngo, PhD – Pharma Industry
Presenting Author: Leock Y Ngo, PhD – Pharma Industry
Claudio Liguori, MD, PhD – Sleep and Epilepsy Center, University Hospital of Rome Tor Vergata, Rome, Italy; Leock Y. Ngo, PhD – Eisai Inc., Nutley, NJ, US; Anna Patten, PhD – Eisai Europe Ltd., Hatfield, UK
Rationale:
Daytime sleepiness is common among patients with epilepsy, affecting quality of life. Anti-seizure medications (ASMs) may improve sleep by reducing seizure frequency, but certain ASMs, such as benzodiazepines (clonazepam), phenobarbital, and valproic acid, may increase the likelihood of daytime sleepiness (Liguori C et al. Sleep Med Rev. 2021;60:101559). Perampanel is approved in > 70 countries and territories including Japan, the United States, China, and other countries in Europe and Asia. AMPA (NCT04257604; Study 501) was a prospective, observational study to evaluate the effectiveness and safety of adjunctive perampanel following ≤ 12-month treatment in routine care in Italy. We present data from AMPA on the effect of perampanel on daytime sleepiness and seizure control.
Methods:
Adult and adolescent patients (aged ≥ 12 years) with insufficiently controlled focal-onset seizures, with/without focal to bilateral tonic-clonic seizures, were prescribed adjunctive perampanel per the approved indication in addition to 1–3 baseline ASMs. The decision to prescribe perampanel was made before, and independently of, the treating physician’s decision to include the patient in AMPA. The Full Analysis Set included patients aged ≥ 18 years from the Safety Analysis Set (including patients receiving ≥ 1 dose of perampanel) who had baseline Epworth Sleepiness Scale (ESS) scores. Daytime sleepiness was assessed using ESS at baseline and end of treatment (EoT; ≤ 12 months). Each of the eight ESS items was scored on a 4-point scale (0–3); total scores ranged from 0–24 with a higher score indicating increased sleepiness. A ≥ 4‑point change from baseline in ESS total score was deemed clinically relevant.
Results:
The Full Analysis Set included 202 adult patients: median (range) age was 40 (18–84) years with most adults (85.1%) aged < 60 years. At EoT, 29 patients reported clinically relevant improvements and 31 patients reported clinically relevant worsening of daytime sleepiness; median percent reductions in seizure frequency/28 days from baseline were 85.6% in the group with improvements vs 77.6% in the group with worsening (n=14 each). Table 1 presents the 50% responder and seizure-freedom rates in patients reporting a baseline 3-point score in response to an ESS item, stratified by baseline characteristics. Trends in seizure control following perampanel treatment varied across ESS items and baseline characteristics. Treatment-emergent adverse events (TEAEs) occurred in 56.9% (n=115/202) of patients (Table 2). The most common TEAEs were dizziness/vertigo (22.8% [n=46/202]) and somnolence (8.4% [n=17/202]).
Conclusions:
Daytime sleepiness was affected positively and negatively in patients receiving adjunctive perampanel. Reductions in seizure frequency/28 days at EoT were higher in patients with improvement in daytime sleepiness, though no consistent trends of shift in daytime sleepiness were identified. No new safety signals emerged.
Funding:
Eisai S.r.l.