Rationale:
In the US, perampanel is approved for the treatment of partial-onset seizures (POS; adjunctive and monotherapy) in patients aged ≥4 years, and as adjunctive treatment of primary generalized tonic-clonic seizures (PGTCS) in patients aged ≥12 years. Study 311 (E2007-G000-311; NCT02849626) was a Phase 3, multicenter, open-label single-arm study of adjunctive perampanel oral suspension in pediatric patients (aged 4 to < 12 years) with POS (with/without secondarily generalized seizures [SGS]) or PGTCS. HRQoL, as measured by the EuroQoL 5-Dimension Youth (EQ-5D-Y) questionnaire, was an exploratory endpoint: initially analysed through simple descriptive summaries. The aim of this post-hoc analysis is to provide a more thorough assessment of HRQoL in paediatric subjects receiving perampanel, including comparisons by seizure type, age, use of enzyme-inducing antiseizure medications (EIASMs) and changes in seizure frequency.
Method:
The Core Study comprised 4-week Pretreatment and 23-week Treatment (11-week Titration; 12-week Maintenance) Periods, followed by Follow-up and/or Extension Periods. This analysis focused on EQ-5D-Y data collected at Baseline and Week 23 (July 2018 data cut). Individual dimensions, visual analogue scale (VAS) and summed misery index (MI) were evaluated at all visits and compared by seizure type (POS versus PGTCS), age (4 to < 7 versus 7 to < 12) and use of concomitant EIASMs (yes versus no). Paretian Classification of Health Change (PCHC) analysis summarised the proportion of subjects who showed improvement or deterioration in HRQoL. Waterfall plots assessed changes in EQ-5D-Y scores by reduction in seizure frequency. Results115 subjects completed EQ-5D-Y at relevant study visits (Seizure type: POS n=84 [of which 21 had SGS], PGTCS n=31; Age: 4 to < 7 years n=30, 7 to < 12 years n=85; Concomitant EIASMs: Yes n=35, No n=80). Completion rate out of those expected to complete EQ-5D-Y at Week 23 was 84.4%. Overall, VAS/MI remained stable over time (did not exceed minimal important difference [MID]) and mean changes from baseline to Week 23 were similar according to seizure type, age and EIASM usage (Table 1). PCHC analysis showed fewer POS subjects experienced deterioration in EQ-5D-Y than PGTCS subjects at Week 23 (25.9% versus 47.4%). More seizure free subjects had improvements in VAS scores compared to those still experiencing seizures at Week 23.
Conclusion:
An in-depth analysis of EQ-5D-Y data allowed for a more nuanced exploration of HRQoL in subjects experiencing seizures than when looking at change from baseline alone. Our findings provide evidence that perampanel as adjunctive therapy did not result in deterioration of patient HRQoL.
Funding:
:This work was funded by Eisai.
FIGURES
Figure 1