The Role of Centralized Reading of Endoscopy in a Randomized Controlled Trial of Mesalamine for Ulcerative Colitis

Brian G Feagan; William J Sandborn; Geert D'Haens; Suresh Pola; John W D McDonald; Paul Rutgeerts; Pia Munkholm; Ulrich Mittmann; Debra King; Cindy J Wong; Guangyong Zou; Allan Donner; Lisa M Shackelton; Denise Gilgen; Sigrid Nelson; Margaret K Vandervoort; Marianne Fahmy; Edward V Loftus; Remo Panaccione; Simon P Travis; Gert A Van Assche; Séverine Vermeire; Barrett G Levesque

doi:10.1053/j.gastro.2013.03.025

The Role of Centralized Reading of Endoscopy in a Randomized Controlled Trial of Mesalamine for Ulcerative Colitis

Brian G Feagan, William J Sandborn, Geert D'Haens, Suresh Pola, John W D McDonald, Paul Rutgeerts, Pia Munkholm, Ulrich Mittmann, Debra King, Cindy J Wong, Guangyong Zou, Allan Donner, Lisa M Shackelton, Denise Gilgen, Sigrid Nelson, Margaret K Vandervoort, Marianne Fahmy, Edward V Loftus, Remo Panaccione, Simon P TravisGert A Van Assche, Séverine Vermeire, Barrett G Levesque

Department of Clinical Medicine

135 Citations (Scopus)

Abstract

Background & Aims: Interobserver differences in endoscopic assessments contribute to variations in rates of response to placebo in ulcerative colitis (UC) trials. We investigated whether centralized review of images could reduce these variations. Methods: We performed a 10-week, randomized, double-blind, placebo-controlled study of 281 patients with mildly to moderately active UC, defined by an Ulcerative Colitis Disease Activity Index (UCDAI) sigmoidoscopy score ≥2, that evaluated the efficacy of delayed-release mesalamine (Asacol 800-mg tablet) 4.8 g/day. Endoscopic images were reviewed by a single expert central reader. The primary outcome was clinical remission (UCDAI, stool frequency and bleeding scores of 0, and no fecal urgency) at week 6. Results: The primary outcome was achieved by 30.0% of patients treated with mesalamine and 20.6% of those given placebo, a difference of 9.4% (95% confidence interval [CI], -0.7% to 19.4%; P =.069). Significant differences in results from secondary analyses indicated the efficacy of mesalamine. Thirty-one percent of participants, all of whom had a UCDAI sigmoidoscopy score ≥2 as read by the site investigator, were considered ineligible by the central reader. After exclusion of these patients, the remission rates were 29.0% and 13.8% in the mesalamine and placebo groups, respectively (difference of 15%; 95% CI, 3.5%-26.0%; P =.011). Conclusions: Although mesalamine 4.8 g/day was not statistically different from placebo for induction of remission in patients with mildly to moderately active UC, based on an intent-to-treat analysis, the totality of the data supports a benefit of treatment. Central review of endoscopic images is critical to the conduct of induction studies in UC; ClinicalTrials.gov Number, NCT01059344.

Original language	English
Journal	Gastroenterology
Volume	145
Issue number	1
Pages (from-to)	149-157.e2
Number of pages	9
ISSN	0016-5085
DOIs	https://doi.org/10.1053/j.gastro.2013.03.025
Publication status	Published - 1 Jul 2013

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Feagan, B. G., Sandborn, W. J., D'Haens, G., Pola, S., McDonald, J. W. D., Rutgeerts, P., Munkholm, P., Mittmann, U., King, D., Wong, C. J., Zou, G., Donner, A., Shackelton, L. M., Gilgen, D., Nelson, S., Vandervoort, M. K., Fahmy, M., Loftus, E. V., Panaccione, R., ... Levesque, B. G. (2013). The Role of Centralized Reading of Endoscopy in a Randomized Controlled Trial of Mesalamine for Ulcerative Colitis. Gastroenterology, 145(1), 149-157.e2. https://doi.org/10.1053/j.gastro.2013.03.025

Feagan, BG, Sandborn, WJ, D'Haens, G, Pola, S, McDonald, JWD, Rutgeerts, P, Munkholm, P, Mittmann, U, King, D, Wong, CJ, Zou, G, Donner, A, Shackelton, LM, Gilgen, D, Nelson, S, Vandervoort, MK, Fahmy, M, Loftus, EV, Panaccione, R, Travis, SP, Van Assche, GA, Vermeire, S & Levesque, BG 2013, 'The Role of Centralized Reading of Endoscopy in a Randomized Controlled Trial of Mesalamine for Ulcerative Colitis', Gastroenterology, vol. 145, no. 1, pp. 149-157.e2. https://doi.org/10.1053/j.gastro.2013.03.025

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title = "The Role of Centralized Reading of Endoscopy in a Randomized Controlled Trial of Mesalamine for Ulcerative Colitis",

abstract = "Background & Aims: Interobserver differences in endoscopic assessments contribute to variations in rates of response to placebo in ulcerative colitis (UC) trials. We investigated whether centralized review of images could reduce these variations. Methods: We performed a 10-week, randomized, double-blind, placebo-controlled study of 281 patients with mildly to moderately active UC, defined by an Ulcerative Colitis Disease Activity Index (UCDAI) sigmoidoscopy score ≥2, that evaluated the efficacy of delayed-release mesalamine (Asacol 800-mg tablet) 4.8 g/day. Endoscopic images were reviewed by a single expert central reader. The primary outcome was clinical remission (UCDAI, stool frequency and bleeding scores of 0, and no fecal urgency) at week 6. Results: The primary outcome was achieved by 30.0% of patients treated with mesalamine and 20.6% of those given placebo, a difference of 9.4% (95% confidence interval [CI], -0.7% to 19.4%; P =.069). Significant differences in results from secondary analyses indicated the efficacy of mesalamine. Thirty-one percent of participants, all of whom had a UCDAI sigmoidoscopy score ≥2 as read by the site investigator, were considered ineligible by the central reader. After exclusion of these patients, the remission rates were 29.0% and 13.8% in the mesalamine and placebo groups, respectively (difference of 15%; 95% CI, 3.5%-26.0%; P =.011). Conclusions: Although mesalamine 4.8 g/day was not statistically different from placebo for induction of remission in patients with mildly to moderately active UC, based on an intent-to-treat analysis, the totality of the data supports a benefit of treatment. Central review of endoscopic images is critical to the conduct of induction studies in UC; ClinicalTrials.gov Number, NCT01059344.",

author = "Feagan, {Brian G} and Sandborn, {William J} and Geert D'Haens and Suresh Pola and McDonald, {John W D} and Paul Rutgeerts and Pia Munkholm and Ulrich Mittmann and Debra King and Wong, {Cindy J} and Guangyong Zou and Allan Donner and Shackelton, {Lisa M} and Denise Gilgen and Sigrid Nelson and Vandervoort, {Margaret K} and Marianne Fahmy and Loftus, {Edward V} and Remo Panaccione and Travis, {Simon P} and {Van Assche}, {Gert A} and S{\'e}verine Vermeire and Levesque, {Barrett G}",

year = "2013",

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doi = "10.1053/j.gastro.2013.03.025",

language = "English",

volume = "145",

pages = "149--157.e2",

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number = "1",

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TY - JOUR

T1 - The Role of Centralized Reading of Endoscopy in a Randomized Controlled Trial of Mesalamine for Ulcerative Colitis

AU - Feagan, Brian G

AU - Sandborn, William J

AU - D'Haens, Geert

AU - Pola, Suresh

AU - McDonald, John W D

AU - Rutgeerts, Paul

AU - Munkholm, Pia

AU - Mittmann, Ulrich

AU - King, Debra

AU - Wong, Cindy J

AU - Zou, Guangyong

AU - Donner, Allan

AU - Shackelton, Lisa M

AU - Gilgen, Denise

AU - Nelson, Sigrid

AU - Vandervoort, Margaret K

AU - Fahmy, Marianne

AU - Loftus, Edward V

AU - Panaccione, Remo

AU - Travis, Simon P

AU - Van Assche, Gert A

AU - Vermeire, Séverine

AU - Levesque, Barrett G

PY - 2013/7/1

Y1 - 2013/7/1

N2 - Background & Aims: Interobserver differences in endoscopic assessments contribute to variations in rates of response to placebo in ulcerative colitis (UC) trials. We investigated whether centralized review of images could reduce these variations. Methods: We performed a 10-week, randomized, double-blind, placebo-controlled study of 281 patients with mildly to moderately active UC, defined by an Ulcerative Colitis Disease Activity Index (UCDAI) sigmoidoscopy score ≥2, that evaluated the efficacy of delayed-release mesalamine (Asacol 800-mg tablet) 4.8 g/day. Endoscopic images were reviewed by a single expert central reader. The primary outcome was clinical remission (UCDAI, stool frequency and bleeding scores of 0, and no fecal urgency) at week 6. Results: The primary outcome was achieved by 30.0% of patients treated with mesalamine and 20.6% of those given placebo, a difference of 9.4% (95% confidence interval [CI], -0.7% to 19.4%; P =.069). Significant differences in results from secondary analyses indicated the efficacy of mesalamine. Thirty-one percent of participants, all of whom had a UCDAI sigmoidoscopy score ≥2 as read by the site investigator, were considered ineligible by the central reader. After exclusion of these patients, the remission rates were 29.0% and 13.8% in the mesalamine and placebo groups, respectively (difference of 15%; 95% CI, 3.5%-26.0%; P =.011). Conclusions: Although mesalamine 4.8 g/day was not statistically different from placebo for induction of remission in patients with mildly to moderately active UC, based on an intent-to-treat analysis, the totality of the data supports a benefit of treatment. Central review of endoscopic images is critical to the conduct of induction studies in UC; ClinicalTrials.gov Number, NCT01059344.

AB - Background & Aims: Interobserver differences in endoscopic assessments contribute to variations in rates of response to placebo in ulcerative colitis (UC) trials. We investigated whether centralized review of images could reduce these variations. Methods: We performed a 10-week, randomized, double-blind, placebo-controlled study of 281 patients with mildly to moderately active UC, defined by an Ulcerative Colitis Disease Activity Index (UCDAI) sigmoidoscopy score ≥2, that evaluated the efficacy of delayed-release mesalamine (Asacol 800-mg tablet) 4.8 g/day. Endoscopic images were reviewed by a single expert central reader. The primary outcome was clinical remission (UCDAI, stool frequency and bleeding scores of 0, and no fecal urgency) at week 6. Results: The primary outcome was achieved by 30.0% of patients treated with mesalamine and 20.6% of those given placebo, a difference of 9.4% (95% confidence interval [CI], -0.7% to 19.4%; P =.069). Significant differences in results from secondary analyses indicated the efficacy of mesalamine. Thirty-one percent of participants, all of whom had a UCDAI sigmoidoscopy score ≥2 as read by the site investigator, were considered ineligible by the central reader. After exclusion of these patients, the remission rates were 29.0% and 13.8% in the mesalamine and placebo groups, respectively (difference of 15%; 95% CI, 3.5%-26.0%; P =.011). Conclusions: Although mesalamine 4.8 g/day was not statistically different from placebo for induction of remission in patients with mildly to moderately active UC, based on an intent-to-treat analysis, the totality of the data supports a benefit of treatment. Central review of endoscopic images is critical to the conduct of induction studies in UC; ClinicalTrials.gov Number, NCT01059344.

U2 - 10.1053/j.gastro.2013.03.025

DO - 10.1053/j.gastro.2013.03.025

M3 - Journal article

C2 - 23528626

SN - 0016-5085

VL - 145

SP - 149-157.e2

JO - Gastroenterology

JF - Gastroenterology

IS - 1

ER -

The Role of Centralized Reading of Endoscopy in a Randomized Controlled Trial of Mesalamine for Ulcerative Colitis

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