Dupilumab Benefits Esophageal Feature Scores in Children with EoE

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At week 52 of the Phase 3 EoE KIDS trial, higher exposure dupilumab significantly improved the endoscopic reference score in children with EoE.

Dupilumab Benefits Esophageal Feature Scores in Children with EoE | Image Credit: Charlein Gracia/Unsplash

Credit: Charlein Gracia/Unsplash

Higher exposure dupilumab led to a significant improvement in the Endoscopic Reference Score (EREFS) for children with eosinophilic esophagitis (EoE), according to new 52-week EoE KIDS data presented at Digestive Disease Week (DDW) 2024.1

EREFS is a validated method for assessment of the major esophageal features of EoE — edema, rings, exudates, furrows, and strictures — that includes subscores to assess inflammation and remodeling.2

“Higher exposure dupilumab significantly improved EREFS total score, inflammation, and the proportion of patients achieving endoscopic remission at week 16. Benefits were maintained to week 52 with continued dupilumab treatment,” said Allen Radin, MD, an executive director of early clinical development and experimental sciences at Regeneron Pharmaceuticals.1

In Part A of EoE Kids, patients were randomized 2:2:1:1 to dupilumab higher-exposure or lower exposure, or placebo, for 16 weeks. Those who completed Part A were eligible to enter Part B, where the dupilumab cohorts remained on their regimen and the placebo group switched to a preassigned dupilumab regimen for 36 weeks.

This analysis of the phase 3 EoE Kids trial sought to evaluate the impact of dupilumab on EREFS, including total score and subscores, in pediatric patients aged 1 to <12 years with active EoE in the trial.

The utility of EREFS has extended to the evaluation of disease activity and treatment response for children with EoE. However, remodeling components are known to be less common in children. A total of 102 children were enrolled in EoE KIDS, including 37 treated with higher-exposure dupilumab, 31 with lower-exposure dupilumab, and 34 with placebo.

EREFS total score was determined as the sum of edema (range, 0–1), rings (range, 0–3), exudates (0–2), furrows (0–2), and strictures (0–1) in the distal and proximal (0–9) regions. The absolute change from baseline in centralized EREFS total score (0–18), and EREFS inflammation (0–10) and remodeling (0–8) subscores at Week 16 and Week 52.

Baseline EREFS total scores were 7.3 and 6.8 in the placebo and dupilumab higher exposure groups, respectively. Inflammatory scores at baseline (placebo: 6.3; dupilumab higher exposure: 5.9) were higher than the remodeling scores (placebo: 1.0; dupilumab higher exposure, 0.9).

Moreover, at baseline, no patients in the placebo group and 2.7% in the dupilumab higher-exposure group exhibited an EREFs total score of 0, 2.9%, and 5.4% an EREFS score of ≤2, and 8.8% and 16.3% an EREFS score of ≤4, respectively.

Upon analysis, the EREFS total score was significantly reduced at Week 16 with dupilumab higher exposure versus placebo (least-squares mean change, –3.5 vs. 0.3; least-squares mean difference, –3.8 [95% CI, –4.9 to –2.6]; P <.001). The improvements in the higher-exposure dupilumab cohort were maintained through Week 52 (mean change from Part A baseline, –4.8) and those switching from placebo to higher-exposure dupulimab experienced an improvement at the same time point (–3.6).

Inflammation subscores were also reduced at Week 16 with dupilumab higher exposure versus placebo (mean change from baseline, –3.5 vs. 0.1; nominal P <.0001). The improvement in inflammation was sustained through Week 52 in the continuous higher-exposure duplilumab group (mean change, –4.2). Those switching from placebo to dupilumab higher exposure in Part B also saw improvement at Week 52 (mean change, –3.2).

Although the lower-exposure dupilumab maintained improvement in endoscopic measures at 52 weeks of treatment, the effects were generally comparable or numerically lower compared with higher exposure dupilumab. Investigators indicated, as anticipated, the assessment of changes in remodeling (–0.2 vs. –0.2 at Week 16) remained limited by the low prevalence of fibrostenotic in young children.

References

  1. Dupilumab Improves Esophageal Features of Eosinophilic Esophagitis (EoE) as Measured By Endoscopic Reference Score in Children with EoE: 52-Week Results from the Phase 3 EoE Kids Trial. ePoster presented at Digestive Disease Week 2024, May 18 - 21, 2024.
  2. Hirano I, Moy N, Heckman MG, Thomas CS, Gonsalves N, Achem SR. Endoscopic assessment of the oesophageal features of eosinophilic oesophagitis: validation of a novel classification and grading system. Gut. 2013;62(4):489-495. doi:10.1136/gutjnl-2011-301817
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