Reliability and responsiveness of endoscopic disease activity assessment in eosinophilic esophagitis

Christopher Ma; Albert J Bredenoord; Evan S Dellon; Jeffrey A Alexander; Luc Biedermann; Malcolm Hogan; Leonardo Guizzetti; Guangyong Zou; David A Katzka; Mirna Chehade; Gary W Falk; Glenn T Furuta; Sandeep K Gupta; Amir F Kagalwalla; Alain M Schoepfer; Stephan Miehlke; Fouad J Moawad; Kathryn Peterson; Nirmala P Gonsalves; Alex Straumann; Joshua B Wechsler; Julie Rémillard; Lisa M Shackelton; Hector S Almonte; Brian G Feagan; Vipul Jairath; Ikuo Hirano

doi:10.1016/j.gie.2022.01.014

Reliability and responsiveness of endoscopic disease activity assessment in eosinophilic esophagitis

Gastrointest Endosc. 2022 Jun;95(6):1126-1137.e2. doi: 10.1016/j.gie.2022.01.014. Epub 2022 Feb 1.

Authors

Christopher Ma¹, Albert J Bredenoord², Evan S Dellon³, Jeffrey A Alexander⁴, Luc Biedermann⁵, Malcolm Hogan⁶, Leonardo Guizzetti⁶, Guangyong Zou⁷, David A Katzka⁴, Mirna Chehade⁸, Gary W Falk⁹, Glenn T Furuta¹⁰, Sandeep K Gupta¹¹, Amir F Kagalwalla¹², Alain M Schoepfer¹³, Stephan Miehlke¹⁴, Fouad J Moawad¹⁵, Kathryn Peterson¹⁶, Nirmala P Gonsalves¹⁷, Alex Straumann¹⁸, Joshua B Wechsler¹⁹, Julie Rémillard⁶, Lisa M Shackelton⁶, Hector S Almonte¹⁷, Brian G Feagan²⁰, Vipul Jairath²⁰, Ikuo Hirano¹⁷

Affiliations

¹ Division of Gastroenterology & Hepatology, Departments of Medicine and Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Alimentiv Inc, London, Ontario, Canada.
² Department of Gastroenterology & Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
³ Division of Gastroenterology and Hepatology, Department of Medicine, Center for Esophageal Diseases and Swallowing, Center for Gastrointestinal Biology and Disease, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
⁴ Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.
⁵ Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.
⁶ Alimentiv Inc, London, Ontario, Canada.
⁷ Alimentiv Inc, London, Ontario, Canada; Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada.
⁸ Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁹ Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
¹⁰ Digestive Health Institute, Children's Hospital Colorado, Gastrointestinal Eosinophilic Diseases Program, University of Colorado School of Medicine, Aurora, Colorado, USA.
¹¹ Division of Pediatric Gastroenterology, Hepatology and Nutrition, Riley Children's Hospital, Indiana University School of Medicine, Community Health Network, Indianapolis, Indiana, USA.
¹² Division of Gastroenterology, Hepatology & Nutrition, Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA; Division of Pediatric Gastroenterology, Department of Pediatrics, John H. Stroger Hospital of Cook County, Chicago, Illinois, USA.
¹³ Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
¹⁴ Center for Esophageal Diseases, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
¹⁵ Division of Gastroenterology, Scripps Clinic, La Jolla, California, USA.
¹⁶ Division of Gastroenterology and Hepatology, University of Utah, Salt Lake City, Utah, USA.
¹⁷ Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
¹⁸ Swiss EoE Clinics and Research Network, Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.
¹⁹ Division of Gastroenterology, Hepatology & Nutrition, Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA.
²⁰ Alimentiv Inc, London, Ontario, Canada; Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada; Division of Gastroenterology and Hepatology, Western University, London, Ontario, Canada.

PMID: 35120883
DOI: 10.1016/j.gie.2022.01.014

Abstract

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.

MeSH terms

Eosinophilic Esophagitis* / diagnosis
Esophagoscopy / methods
Humans
Proton Pump Inhibitors
Reproducibility of Results
Severity of Illness Index

Substances

Proton Pump Inhibitors