EREFS as a Clinical Trial Endpoint in Eosinophilic Oesophagitis

Introduction:

Eosinophilic oesophagitis (EoE) is a chronic immune-mediated condition that significantly contributes to upper gastrointestinal morbidity. Historically, clinical trials evaluating treatments for EoE have relied on two co-primary endpoints: symptom improvement and histologic assessment, primarily measured by peak eosinophil count (PEC). While PEC has been widely used as an objective biomarker of disease activity, it has limitations in fully capturing the global severity and activity of EoE. Endoscopic evaluation, particularly through the Hirano EoE Endoscopic Reference Score (EREFS), has emerged as a promising outcome metric that offers a more comprehensive assessment of disease activity. This review explores the potential of EREFS as a "trial-ready" endpoint, alongside or in place of PEC, in clinical trials for EoE.

Problem Statement:

The current reliance on PEC as a primary histologic endpoint in EoE clinical trials may not fully encapsulate the complexity of disease activity or its impact on the oesophagus. PEC provides a snapshot of eosinophilic infiltration but does not reflect structural changes, complications, or the broader severity of the disease. On the other hand, endoscopic findings, as classified by the EREFS system, provide a standardized and validated method to assess key oesophageal features such as rings, furrows, exudates, edema, and strictures. EREFS has demonstrated accuracy, responsiveness, and clinical relevance, making it a strong candidate for inclusion as a co-primary or standalone endpoint in EoE trials. However, its integration into clinical trials requires further exploration and consensus on defined thresholds for response and its association with clinically meaningful outcomes.

Conclusion:

The Hirano EoE Endoscopic Reference Score (EREFS) offers a validated and standardized approach to assessing oesophageal disease activity and severity in eosinophilic oesophagitis. Evidence supports its accuracy, responsiveness to therapy, and clinical relevance, making it a viable and "trial-ready" endpoint for clinical trials. While PEC remains an important measure of histologic response, EREFS provides a complementary perspective that encompasses structural and functional changes in the oesophagus. Incorporating EREFS as a co-primary biologic endpoint in EoE trials could enhance the evaluation of therapeutic efficacy and provide a more comprehensive understanding of disease activity. This approach has the potential to improve clinical care and advance the development of effective treatments for EoE.