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Reliability and responsiveness of endoscopic disease activity assessment in eosinophilic esophagitis

Published:February 01, 2022DOI:https://doi.org/10.1016/j.gie.2022.01.014

      Background and Aims

      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.

      Methods

      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).

      Results

      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.

      Conclusions

      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.

      Graphical abstract

      Abbreviations:

      AUC (area under the receiver-operating characteristic curve), EoE (eosinophilic esophagitis), EREFS (Eosinophilic Esophagitis Endoscopic Reference Score), ICC (intraclass correlation coefficient), RAM (Research and Development University of California Los Angeles appropriateness methodology), RCT (randomized controlled trial), SD (standard deviation), SES (standardized effect size), VAS (visual analog scale)
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      References

        • de Rooij W.E.
        • Dellon E.S.
        • Parker C.E.
        • et al.
        Pharmacotherapies for the treatment of eosinophilic esophagitis: state of the art review.
        Drugs. 2019; 79: 1419-1434
        • Lyons E.
        • Donohue K.
        • Lee J.J.
        Developing pharmacologic treatments for eosinophilic esophagitis: draft guidance from the United States Food and Drug Administration.
        Gastroenterology. 2019; 157: 275-277
        • Ma C.
        • Schoepfer A.M.
        • Dellon E.S.
        • et al.
        Development of a core outcome set for therapeutic studies in eosinophilic esophagitis (COREOS).
        J Allergy Clin Immunol. 2022; 149: 659-670
        • Kim H.P.
        • Vance R.B.
        • Shaheen N.J.
        • et al.
        The prevalence and diagnostic utility of endoscopic features of eosinophilic esophagitis: a meta-analysis.
        Clin Gastroenterol Hepatol. 2012; 10: 988-996
        • Hirano I.
        • Moy N.
        • Heckman M.G.
        • et al.
        Endoscopic assessment of the oesophageal features of eosinophilic oesophagitis: validation of a novel classification and grading system.
        Gut. 2013; 62: 489-495
        • Ma C.
        • van Rhijn B.D.
        • Jairath V.
        • et al.
        Heterogeneity in clinical, endoscopic, and histologic outcome measures and placebo response rates in clinical trials of eosinophilic esophagitis: a systematic review.
        Clin Gastroenterol Hepatol. 2018; 16: 1714-1729
        • Dellon E.S.
        • Cotton C.C.
        • Gebhart J.H.
        • et al.
        Accuracy of the eosinophilic esophagitis endoscopic reference score in diagnosis and determining response to treatment.
        Clin Gastroenterol Hepatol. 2016; 14: 31-39
        • Schoepfer A.M.
        • Hirano I.
        • Coslovsky M.
        • et al.
        Variation in endoscopic activity assessment and endoscopy score validation in adults with eosinophilic esophagitis.
        Clin Gastroenterol Hepatol. 2019; 17: 1477-1488
        • Fitch K.
        • Bernstein S.
        • Aguilar M.
        • et al.
        The RAND/UCLA appropriateness method user’s manual.
        RAND Corporation, Santa Monica, CA2001
        • Warners M.J.
        • Hindryckx P.
        • Levesque B.G.
        • et al.
        Systematic review: disease activity indices in eosinophilic esophagitis.
        Am J Gastroenterol. 2017; 112: 1658-1669
        • U.S. Food and Drug Administration
        Center for Drug Evaluation and Research: clinical outcome assessment (COA) compendium.
        2021 (Available at: https://www.fda.gov/drugs/development-resources/clinical-outcome-assessment-compendium. Accessed February 27, 2021)
        • Landis J.R.
        • Koch G.G.
        The measurement of observer agreement for categorical data.
        Biometrics. 1977; 33: 159-174
        • Fleiss J.L.
        • Cohen J.
        The equivalence of weighted kappa and the intraclass correlation coefficient as measures of reliability.
        Educ Psychol Measure. 1973; 33: 613-619
        • Berk R.A.
        Generalizability of behavioral observations: a clarification of interobserver agreement and interobserver reliability.
        Am J Ment Defic. 1979; 83: 460-472
        • Norman G.R.
        • Sloan J.A.
        • Wyrwich K.W.
        Interpretation of changes in health-related quality of life: the remarkable universality of half a standard deviation.
        Med Care. 2003; 41: 582-592
        • Marchal-Bressenot A.
        • Salleron J.
        • Boulagnon-Rombi C.
        • et al.
        Development and validation of the Nancy histological index for UC.
        Gut. 2017; 66: 43-49
        • Mosli M.H.
        • Feagan B.G.
        • Zou G.
        • et al.
        Development and validation of a histological index for UC.
        Gut. 2017; 66: 50-58
        • Hindryckx P.
        • Jairath V.
        • Zou G.
        • et al.
        Development and validation of a magnetic resonance index for assessing fistulas in patients with Crohn's disease.
        Gastroenterology. 2019; 157: 1233-1244
        • Jairath V.
        • Ordas I.
        • Zou G.
        • et al.
        Reliability of measuring ileo-colonic disease activity in Crohn's disease by magnetic resonance enterography.
        Inflamm Bowel Dis. 2018; 24: 440-449
        • Cohen J.
        A power primer.
        Psychol Bull. 1992; 112: 155-159
        • Safroneeva E.
        • Straumann A.
        • Coslovsky M.
        • et al.
        Symptoms have modest accuracy in detecting endoscopic and histologic remission in adults with eosinophilic esophagitis.
        Gastroenterology. 2016; 150: 581-590
        • Ma C.
        • Schoepfer A.M.
        • Safroneeva E.
        • et al.
        Development of a Core Outcome Set for Therapeutic Studies in Eosinophilic Esophagitis (COREOS): an international multidisciplinary consensus.
        Gastroenterology. 2021; 161: 748-755
        • Zou G.Y.
        Sample size formulas for estimating intraclass correlation coefficients with precision and assurance.
        Stat Med. 2012; 31: 3972-3981
        • Ishimura N.
        • Sumi S.
        • Okada M.
        • et al.
        Ankylosaurus back sign: novel endoscopic finding in esophageal eosinophilia patients indicating proton pump inhibitor response.
        Endosc Int Open. 2018; 6: E165-E172
        • van Rhijn B.D.
        • Warners M.J.
        • Curvers W.L.
        • et al.
        Evaluating the endoscopic reference score for eosinophilic esophagitis: moderate to substantial intra- and interobserver reliability.
        Endoscopy. 2014; 46: 1049-1055
        • Khanna R.
        • Zou G.
        • D'Haens G.
        • et al.
        Reliability among central readers in the evaluation of endoscopic findings from patients with Crohn's disease.
        Gut. 2016; 65: 1119-1125
        • Lee J.
        • Huprich J.
        • Kujath C.
        • et al.
        Esophageal diameter is decreased in some patients with eosinophilic esophagitis and might increase with topical corticosteroid therapy.
        Clin Gastroenterol Hepatol. 2012; 10: 481-486
        • Read A.J.
        • Pandolfino J.E.
        Biomechanics of esophageal function in eosinophilic esophagitis.
        J Neurogastroenterol Motil. 2012; 18: 357-364
        • Schoepfer A.M.
        • Straumann A.
        • Panczak R.
        • et al.
        Development and validation of a symptom-based activity index for adults with eosinophilic esophagitis.
        Gastroenterology. 2014; 147: 1255-1266
        • Schoepfer A.M.
        • Safroneeva E.
        • Bussmann C.
        • et al.
        Delay in diagnosis of eosinophilic esophagitis increases risk for stricture formation in a time-dependent manner.
        Gastroenterology. 2013; 145: 1230-1236
        • Wechsler J.B.
        • Bolton S.M.
        • Amsden K.
        • et al.
        Eosinophilic esophagitis reference score accurately identifies disease activity and treatment effects in children.
        Clin Gastroenterol Hepatol. 2018; 16: 1056-1063
        • Dellon E.S.
        • Katzka D.A.
        • Collins M.H.
        • et al.
        Budesonide oral suspension improves symptomatic, endoscopic, and histologic parameters compared with placebo in patients with eosinophilic esophagitis.
        Gastroenterology. 2017; 152: 776-786
        • Hirano I.
        • Collins M.H.
        • Assouline-Dayan Y.
        • et al.
        RPC4046, a monoclonal antibody against IL13, reduces histologic and endoscopic activity in patients with eosinophilic esophagitis.
        Gastroenterology. 2019; 156: 592-603
        • Hirano I.
        • Dellon E.S.
        • Hamilton J.D.
        • et al.
        Efficacy of dupilumab in a phase 2 randomized trial of adults with active eosinophilic esophagitis.
        Gastroenterology. 2020; 158: 111-122
        • Lucendo A.J.
        • Miehlke S.
        • Schlag C.
        • et al.
        Efficacy of budesonide orodispersible tablets as induction therapy for eosinophilic esophagitis in a randomized placebo-controlled trial.
        Gastroenterology. 2019; 157: 74-86
        • Nhu Q.M.
        • Hsieh L.
        • Dohil L.
        • et al.
        Antifibrotic effects of the thiazolidinediones in eosinophilic esophagitis pathologic remodeling: a preclinical evaluation.
        Clin Transl Gastroenterol. 2020; 11: e00164