Review article: Seeing Is Believing–The Eosinophilic Oesophagitis Endoscopic Reference Score Can Serve as a Valuable Clinical Trial Endpoint in Eosinophilic Oesophagitis

BACKGROUND: Eosinophilic oesophagitis (EoE) is a major contributor to upper gastrointestinal morbidity. Although an increasing number of treatment modalities have been developed, most are assessed by symptoms and the histologic metric of peak eosinophil count (PEC). AIM: To review current evidence regarding limitations of reliance on PEC as a co-primary endpoint while making a case for endoscopic assessment as a "trial-ready" outcome to supplement or replace it. METHODS: Directed literature review, including a summary of EoE clinical trials and outcome metrics, combined with expert discussion, input, and consensus on reviewed topics. RESULTS: Clinical trials in EoE established efficacy based on co-primary endpoints of clinically meaningful symptom improvement and PEC as an objective biomarker of activity. However, endoscopic features of EoE have a critical role in determining disease activity. The Hirano EoE Endoscopic Reference Score (EREFS) is a uniform nomenclature system that classifies five key oesophageal findings. EREFS has been validated, shown to be highly accurate and responsive, and incorporated into clinical trials. An association between EREFS and clinically meaningful disease outcomes and complications has been demonstrated, heightening its relevance to clinical care and as a clinical trial endpoint. Defined thresholds for response of EREFS to therapy have been shown to be responsive to therapy. CONCLUSIONS: PEC has a role in histologic response assessment and should not be completely discounted. Evidence demonstrates that EREFS accurately reflects EoE disease activity and global oesophageal severity, and is ready to be used as a co-primary biologic endpoint in clinical trials.