Abstracts

Rationale: LGS is a severe refractory childhood-onset epilepsy characterized by a triad of multiple seizure types (including drop seizures), intellectual disability, and certain electroencephalographic abnormalities. Patients’ health-related quality of life (HRQoL) can be impaired by either persistent seizures or adverse events resulting from treatment for LGS. We report HRQoL results from the Core Study of a Phase III study (Study 338; NCT02834793) that assessed the effect of adjunctive perampanel in patients with uncontrolled seizures associated with LGS.

Methods: Study 338 enrolled patients with clinical and electroencephalogram confirmation of LGS diagnosis with disease onset before 11 years of age, who were receiving 1–4 concomitant anti-seizure medications at stable doses for ≥ 30 days before screening and had an average of ≥ 2 drop seizures/week during baseline. The Core Study was a randomized, double-blind, placebo-controlled phase (4–8-week screening/baseline, 6-week Titration [2–≤ 8 mg/day based on response and tolerability], 12-week Maintenance). Exploratory endpoints included healthcare outcome measures during the Core Study; the effect of perampanel on HRQoL for up to 18 weeks of treatment in patients with LGS was assessed by Euroqol-5 dimension (EQ-5D) index and visual analogue scale (VAS). An increase in VAS score corresponds to an improvement in HRQoL whereas a decrease corresponds to a worsening. EQ-5D-Y or EQ-5D-3L was used for patients aged < 16 years or ≥ 16 years, respectively; the proxy versions of EQ-5D-Y and EQ-5D-3L were completed by caregivers for patients with reading disabilities.

Results: Seventy patients were randomized in the Core Study to receive perampanel (n=34) or placebo (n=36). The proportions of patients reporting no problems, some problems, or a lot of problems in each of the EQ-5D domains at baseline and following 18 weeks’ treatment with perampanel or placebo are shown in Table 1 by age group and reading ability. Among patients aged < 16 years, the mean (standard deviation [SD]) changes in EQ-5D-Y VAS scores, reported by caregivers, were 2.0 (19.0; n=20) with perampanel and 0.4 (12.8; n=18) with placebo, and one patient receiving placebo self-reported a change of ‑10.0 at Week 18. Among patients aged ≥ ‍16 years, the mean (SD) changes in EQ-5D-3L VAS scores, reported by caregivers, were -9.2 (21.8; n=9) with perampanel and 5.6 (12.0; n=7) with placebo; for patients who self-rated HRQoL, the mean (SD) changes were -5.7 (15.0; n=3) with perampanel and ‑3.3 (19.7; n=6) with placebo.

Conclusions: Overall, changes in HRQoL from baseline across all EQ‑5D domains were generally small; proportions of patients reported no/some/a lot of problems in each EQ-5D domain slightly changed during Study 338 Core Study, irrespective of treatment. A trend of worsening in HRQoL from baseline was observed following 18-week treatment with perampanel among patients aged ≥ 16 years based on EQ-5D VAS scores; however, interpretation of these data is limited due to small sample size.

Funding: Eisai Co., Ltd., Eisai Inc., and Eisai Ltd.