Reliability and responsiveness of endoscopic disease activity assessment in eosinophilic esophagitis.

Endoscopic outcomes have become important measures of eosinophilic esophagitis (EoE) disease activity, including as an endpoint in randomized controlled trials (RCTs). We evaluated the operating properties of endoscopic measures for use in EoE RCTs. Modified Research and Development/University of California Los Angeles appropriateness methods and a panel of 15 international EoE experts identified endoscopic items and definitions with face validity that were used in a 2-round voting process to define simplified (all items graded as absent or present) and expanded versions (additional grades for edema, furrows, and/or exudates) of the EoE Endoscopic Reference Score (EREFS). Inter- and intrarater reliability of these instruments (expressed as intraclass correlation coefficients [ICC]) were evaluated using paired endoscopy video assessments of 2 blinded central readers in patients before and after 8 weeks of proton pump inhibitors, swallowed topical corticosteroids, or dietary elimination. Responsiveness was measured using the standardized effect size (SES). The appropriateness of 41 statements relevant to EoE endoscopic activity (endoscopic items, item definitions and grading, and other considerations relevant for endoscopy) was considered. The original and expanded EREFS demonstrated moderate-to-substantial inter-rater reliability (ICCs of .472-.736 and .469-.763, respectively) and moderate-to-almost perfect intrarater reliability (ICCs of .580-.828 and .581-.828, respectively). Strictures were least reliably assessed (ICC, .072-.385). The original EREFS was highly responsive (SES, 1.126 [95% confidence interval {CI}, .757-1.534]), although both expanded versions of EREFS, scored based on worst affected area, were numerically most responsive to treatment (expanded furrows: SES, 1.229 [95% CI, .858-1.643]; all items expanded: SES, 1.252 [95% CI, .880-1.667]). The EREFS and its modifications were not more reliably scored by segment and also not more responsive when proximal and distal EREFSs were summed. EREFS and its modifications were reliable and responsive, and the original or expanded versions of the EREFS may be preferred in RCTs. Disease activity scored based on the worst affected area optimizes reliability and responsiveness

Development of a core outcome set for therapeutic studies in eosinophilic esophagitis (COREOS).

End points used to determine treatment efficacy in eosinophilic esophagitis (EoE) have evolved over time. With multiple novel therapies in development for EoE, harmonization of outcomes measures will facilitate evidence synthesis and appraisal when comparing different treatments. We sought to develop a core outcome set (COS) for controlled and observational studies of pharmacologic and diet interventions in adult and pediatric patients with EoE. Candidate outcomes were generated from systematic literature reviews and patient engagement interviews and surveys. Consensus was established using an iterative Delphi process, with items voted on using a 9-point Likert scale and with feedback from other participants to allow score refinement. Consensus meetings were held to ratify the outcome domains of importance and the core outcome measures. Stakeholders were recruited internationally and included adult and pediatric gastroenterologists, allergists, dieticians, pathologists, psychologists, researchers, and methodologists. The COS consists of 4 outcome domains for controlled and observational studies: histopathology, endoscopy, patient-reported symptoms, and EoE-specific quality of life. A total of 69 stakeholders (response rate 95.8%) prioritized 42 outcomes in a 2-round Delphi process, and the final ratification meeting generated consensus on 33 outcome measures. These included measurement of the peak eosinophil count, Eosinophilic Esophagitis Histology Scoring System, Eosinophilic Esophagitis Endoscopic Reference Score, and patient-reported measures of dysphagia and quality of life. This interdisciplinary collaboration involving global stakeholders has produced a COS that can be applied to adult and pediatric studies of pharmacologic and diet therapies for EoE and will facilitate meaningful treatment comparisons and improve the quality of data synthesis