see related editorial on page x INFLAMMATORY BOWEL DISEASE 1 © 2017 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY ORIGINAL CONTRIBUTIONS Responsiveness of Endoscopic Indices of Disease Activity for Crohn’s Disease Reena Khanna, MD 1, 2 , GuangYong Zou, PhD 1, 3 , Larry Stitt, MSc 1 , Brian G. Feagan, MD 1, 2, 3 , William J. Sandborn, MD 1, 4 , Paul Rutgeerts, MD, PhD 5 , John W.D. McDonald, MD 1 , Elena Dubcenco, MD 1 , Ronald Fogel, MD 6 , Remo Panaccione, MD 7 , Vipul Jairath, MD, PhD 1, 2, 3, 8 , Sigrid Nelson, MSc 1 , Lisa M. Shackelton, PhD 1 , Bidan Huang, PhD 9 , Qian Zhou, PhD 8 , Anne M. Robinson 9 , Barrett G. Levesque, MD 1, 4 and Geert D’Haens, MD, PhD 1, 10 OBJECTIVES: The Crohn’s Disease Endoscopic Index of Severity (CDEIS) and the Simple Endoscopic Score for Crohn’s Disease (SES-CD) are commonly used to assess Crohn’s disease (CD) activity; however neither instrument is fully validated. We evaluated the responsiveness to change of the SES-CD and CDEIS using data from a trial of adalimumab, a drug therapy of known efficacy. METHODS: Paired video recordings ( N=112) of colonoscopies (baseline and week 8–12) obtained from patients with CD who participated in a trial of adalimumab therapy were reviewed in random order, in duplicate, by four central readers (56 pairs of videos by 2 groups of readers). Responsiveness of the SES-CD and the CDEIS was evaluated by comparing correlations between the observed and pre-specified predictions of change scores for these endoscopic indices with a global endoscopic evaluation of severity (GELS), a patient reported outcome (PRO2), and the Crohn’s disease activity index (CDAI), and by calculation of the standardized effect size, and Guyatt’s Responsiveness statistic (GRS) using 2 definitions of change; (1) treatment assignment and (2) an absolute change in total PRO2 of 50. The potential application of effect size estimates was demonstrated by calculating hypothetical sample sizes for comparing two independent groups. The impact of removing stenosis as an index item and adjusting for the number of segments observed was also assessed. RESULTS: Changes in both endoscopic instruments and the GELS were highly correlated. The SES-CD displayed numerically higher effect sizes for both definitions of change. The standardized effect size and GRS estimates (95% confidence interval) for the SES-CD based on treatment assignment were 0.84 (0.53, 1.15) and 0.79 (0.48, 1.09). Corresponding values for the CDEIS were 0.72 (0.42, 1.02) and 0.75 (0.45, 1.06). The standardized effect size and GRS estimates for the SES-CD based on an absolute change in total PRO2 of 50 points or greater were 0.76 (0.49, 1.02) and 0.93 (0.64, 1.21). Corresponding values for CDEIS were 0.70 (0.44, 0.97), 0.83 (0.55, 1.10). Removal of stenosis as an index item and adjusting for observed segments did not improve responsiveness estimates. CONCLUSIONS: Although both the SES-CD and CDEIS are valid measures of endoscopic disease activity that are moderately responsive to changes in endoscopic disease activity, the SES-CD displayed numerically greater responsiveness in this data set. SUPPLEMENTARY MATERIAL is linked to the online version of the paper at http://www.nature.com/ajg Am J Gastroenterol advance online publication, 10 January 2017; doi:10.1038/ajg.2016.580 1 Robarts Clinical Trials, University of Western Ontario, London, Ontario, Canada; 2 Division of Gastroenterology, Department of Medicine, University of Western Ontario, London, Ontario, Canada; 3 Department of Epidemiology and Biostatistics, University of Western Ontario, London, Ontario, Canada; 4 Division of Gastroenterology, University of California San Diego, La Jolla, California, USA; 5 Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium; 6 Digestive Health Center of Michigan, Chesterfield, Michigan, USA; 7 Inflammatory Bowel Disease Clinic, University of Calgary , Calgary, Alberta, Canada; 8 Nuffield Department of Medicine, University of Oxford, Oxford, UK; 9 AbbVie, Inc, North Chicago, Illinois, USA; 10 Inflammatory Bowel Disease Centre, Academic Medical Centre, Amsterdam, The Netherlands. Correspondence: Geert D’Haens, MD, PhD Inflammatory Bowel Disease Centre, Academic Medical Centre, Meibergdreef 9—C2-112, 1105 AZ, Amsterdam, The Netherlands. E-mail: g.dhaens@amc.uva.nl Received 5 July 2016; accepted 17 October 2016