title: The role of centralized reading of endoscopy in a randomized controlled trial of mesalamine for ulcerative colitis.
abstract: OBJECTIVE
  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.
authors.affiliation: Robarts Clinical Trials, Western University, London, Ontario, Canada; Department of Medicine, Western University, London, Ontario, Canada; Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada. Electronic address: bfeagan@robarts.ca.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Feagan
authors.affiliation: UCSD Inflammatory Bowel Disease Center, University of California San Diego, La Jolla, California; Robarts West, La Jolla, California.
authors.forename: William J
authors.initials: WJ
authors.lastname: Sandborn
authors.affiliation: Department of Gastroenterology, Academic Medical Center, and Robarts Europe, Amsterdam, The Netherlands.
authors.forename: Geert
authors.initials: G
authors.lastname: D'Haens
authors.affiliation: UCSD Inflammatory Bowel Disease Center, University of California San Diego, La Jolla, California.
authors.forename: Suresh
authors.initials: S
authors.lastname: Pola
authors.affiliation: Robarts Clinical Trials, Western University, London, Ontario, Canada.
authors.forename: John W D
authors.initials: JWD
authors.lastname: McDonald
authors.affiliation: Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium.
authors.forename: Paul
authors.initials: P
authors.lastname: Rutgeerts
authors.affiliation: Digestive Disease Center, Medical Section, Herlev University Hospital, Herlev, Denmark.
authors.forename: Pia
authors.initials: P
authors.lastname: Munkholm
authors.affiliation: Mittmann Pharma Consulting, Basel, Switzerland.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Mittmann
authors.affiliation: Robarts Clinical Trials, Western University, London, Ontario, Canada.
authors.forename: Debra
authors.initials: D
authors.lastname: King
authors.affiliation: Robarts Clinical Trials, Western University, London, Ontario, Canada.
authors.forename: Cindy J
authors.initials: CJ
authors.lastname: Wong
authors.affiliation: Robarts Clinical Trials, Western University, London, Ontario, Canada; Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada.
authors.forename: Guangyong
authors.initials: G
authors.lastname: Zou
authors.affiliation: Robarts Clinical Trials, Western University, London, Ontario, Canada; Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada.
authors.forename: Allan
authors.initials: A
authors.lastname: Donner
authors.affiliation: Robarts Clinical Trials, Western University, London, Ontario, Canada.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Shackelton
authors.affiliation: Tillotts Pharma AG, Rheinfelden, Switzerland.
authors.forename: Denise
authors.initials: D
authors.lastname: Gilgen
authors.affiliation: Robarts West, La Jolla, California.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Nelson
authors.affiliation: Robarts Clinical Trials, Western University, London, Ontario, Canada.
authors.forename: Margaret K
authors.initials: MK
authors.lastname: Vandervoort
authors.affiliation: UCSD Inflammatory Bowel Disease Center, University of California San Diego, La Jolla, California.
authors.forename: Marianne
authors.initials: M
authors.lastname: Fahmy
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Edward V
authors.initials: EV
authors.lastname: Loftus
authors.affiliation: Inflammatory Bowel Disease Clinic, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Remo
authors.initials: R
authors.lastname: Panaccione
authors.affiliation: Gastroenterology Unit, John Radcliffe Hospital, Oxford, England.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Travis
authors.affiliation: Division of Gastroenterology, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Gert A
authors.initials: GA
authors.lastname: Van Assche
authors.affiliation: Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium.
authors.forename: Séverine
authors.initials: S
authors.lastname: Vermeire
authors.affiliation: UCSD Inflammatory Bowel Disease Center, University of California San Diego, La Jolla, California; Robarts West, La Jolla, California.
authors.forename: Barrett G
authors.initials: BG
authors.lastname: Levesque
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D019804:Mesalamine / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D012812:Sigmoidoscopy
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D019804:Mesalamine