Reena Khanna1,2, GuangYong Zou1,3, Larry Stitt1, Brian G Feagan1,2,3, William J Sandborn1,4, Paul Rutgeerts5, John W D McDonald1, Elena Dubcenco1, Ronald Fogel6, Remo Panaccione7, Vipul Jairath1,2,3,8, Sigrid Nelson1, Lisa M Shackelton1, Bidan Huang9, Qian Zhou8, Anne M Robinson9, Barrett G Levesque1,4, Geert D'Haens1,10. 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.
Abstract
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.
RCT Entities:
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.
Authors: Reena Khanna; Guangyong Zou; Geert D'Haens; Paul Rutgeerts; J W D McDonald; Marco Daperno; Brian G Feagan; William J Sandborn; Elena Dubcenco; Larry Stitt; Margaret K Vandervoort; Allan Donner; Allison Luo; Barrett G Levesque Journal: Gut Date: 2015-05-02 Impact factor: 23.059
Authors: Klaus Gottlieb; Simon Travis; Brian Feagan; Fez Hussain; William J Sandborn; Paul Rutgeerts Journal: Inflamm Bowel Dis Date: 2015-10 Impact factor: 5.325
Authors: R Khanna; G Zou; G D'Haens; B G Feagan; W J Sandborn; M K Vandervoort; R L Rolleri; E Bortey; C Paterson; W P Forbes; B G Levesque Journal: Aliment Pharmacol Ther Date: 2014-10-27 Impact factor: 8.171
Authors: L Peyrin-Biroulet; W Sandborn; B E Sands; W Reinisch; W Bemelman; R V Bryant; G D'Haens; I Dotan; M Dubinsky; B Feagan; G Fiorino; R Gearry; S Krishnareddy; P L Lakatos; E V Loftus; P Marteau; P Munkholm; T B Murdoch; I Ordás; R Panaccione; R H Riddell; J Ruel; D T Rubin; M Samaan; C A Siegel; M S Silverberg; J Stoker; S Schreiber; S Travis; G Van Assche; S Danese; J Panes; G Bouguen; S O'Donnell; B Pariente; S Winer; S Hanauer; J-F Colombel Journal: Am J Gastroenterol Date: 2015-08-25 Impact factor: 10.864
Authors: Elena Dubcenco; Guangyong Zou; Larry Stitt; Jeffrey P Baker; Khursheed N Jeejeebhoy; Gabor Kandel; Young-In Kim; Samir C Grover; John W D McDonald; Lisa M Shackelton; Reena Khanna; Geert D'Haens; William J Sandborn; Brian G Feagan; Barrett G Levesque Journal: J Crohns Colitis Date: 2016-07-06 Impact factor: 9.071
Authors: Christopher Andrew Lamb; Nicholas A Kennedy; Tim Raine; Philip Anthony Hendy; Philip J Smith; Jimmy K Limdi; Bu'Hussain Hayee; Miranda C E Lomer; Gareth C Parkes; Christian Selinger; Kevin J Barrett; R Justin Davies; Cathy Bennett; Stuart Gittens; Malcolm G Dunlop; Omar Faiz; Aileen Fraser; Vikki Garrick; Paul D Johnston; Miles Parkes; Jeremy Sanderson; Helen Terry; Daniel R Gaya; Tariq H Iqbal; Stuart A Taylor; Melissa Smith; Matthew Brookes; Richard Hansen; A Barney Hawthorne Journal: Gut Date: 2019-09-27 Impact factor: 23.059
Authors: Neeraj Narula; Emily C L Wong; Jean-Frederic Colombel; William J Sandborn; Marc Ferrante; John K Marshall; Walter Reinisch; Parambir S Dulai Journal: J Crohns Colitis Date: 2022-05-10 Impact factor: 10.020
Authors: A Therrien; L Chapuy; M Bsat; M Rubio; G Bernard; E Arslanian; K Orlicka; A Weber; B-P Panzini; J Dorais; E-J Bernard; G Soucy; M Bouin; M Sarfati Journal: Clin Exp Immunol Date: 2018-11-28 Impact factor: 4.330
Authors: Joseph Sleiman; Sara El Ouali; Taha Qazi; Benjamin Cohen; Scott R Steele; Mark E Baker; Florian Rieder Journal: Expert Rev Gastroenterol Hepatol Date: 2020-12-28 Impact factor: 3.869
Authors: Klaus Gottlieb; Marco Daperno; Keith Usiskin; Bruce E Sands; Harris Ahmad; Colin W Howden; William Karnes; Young S Oh; Irene Modesto; Colleen Marano; Ryan William Stidham; Walter Reinisch Journal: Gut Date: 2020-07-22 Impact factor: 23.059