S381 Esophageal Eosinophil Count Does Not Correlate With the Endoscopic Reference Score Remodeling Subscore in Placebo-Treated Eosinophilic Esophagitis Patients in the Phase 2 Proof-of-Concept and Phase 3 TREET Studies

Abstract

Introduction: Eosinophilic esophagitis (EoE) is a chronic type 2 inflammatory disease of the esophagus. Although eosinophils (eos) are the hallmark of EoE diagnosis, their exact role in disease is unclear. The EoE-Endoscopic Reference Score (EREFS) assesses severity of endoscopically identified inflammatory (edema, exudate, furrows) and remodeling (rings, strictures) aspects of disease activity. To examine the relationship between eosinophilic inflammation and endoscopic disease activity, correlations were assessed between esophageal intraepithelial eos count (eos/high-power field [hpf]) and EREFS in EoE patients (pts) receiving placebo (PBO) in 2 clinical trials: the 12-week phase 2 proof-of-concept study (POC; NCT02379052) in adults and the 24-week Part A of the 3-part, phase 3 TREET study (P3PA; NCT03633617), in adolescents and adults. Methods: Endoscopies of the proximal and distal esophagus were performed at baseline (BL) and end of treatment (EOT) and scored for inflammatory and remodeling subscores, and total score using EREFS (higher scores indicate greater severity). Eos/hpf was measured from pinch biopsies of proximal, mid, and distal esophagus at BL and EOT. Pearson correlations were performed between eos/hpf and EREFS total, subscores, and components at BL, EOT, and change from BL at EOT. Results: Few strong correlations (correlation coefficient > 0.5) were observed at BL between eos/hpf and EREFS in pts receiving PBO of both studies (Table 1). Moderate-to-strong correlations were observed between EREFS total score and eos/hpf in P3PA, but not POC. Moderate-to-strong correlations were observed in both studies between eos/hpf and the EREFS inflammation subscore and inflammatory components of edema, exudates, and furrows (some of which reached statistical significance). All correlations of eosinophil levels to the EREFS remodeling subscore and rings/stricture components were weak-to-moderate and not statistically significant (P values ranged from 0.07 to 0.94). Conclusion: In these EoE pts, no strong correlations were observed between eos/hpf and endoscopic remodeling as assessed by EREFS. Moderate to strong correlations were observed between eos/hpf and endoscopic markers of inflammation. Combined with histology, endoscopic assessment of remodeling aspects of EoE provides a more comprehensive characterization of disease activity. Further study, with larger sample sizes, is required to verify and validate these findings in other populations, duration of observation, and treatment contexts.Table 1.: Correlations between esophageal intraepithelial eosinophil count (eos/hpf) and EREFS total score, inflammation and remodeling subscores, and individual components scores in patients with EoE receiving placebo in the phase 2 POC study and part A of the phase 3 LIBERTY TREET study.