{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T09:44:49Z","timestamp":1750326289746,"version":"3.37.3"},"reference-count":18,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T00:00:00Z","timestamp":1675814400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>High histologic remission rates have been reported with placebos in randomized controlled trials (RCTs) evaluating ulcerative colitis (UC) therapies and have varied based on trial designs. We performed a systematic review and meta-analysis to quantify placebo histological remission rates and identify factors influencing those rates.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>MEDLINE, EMBASE, and the Cochrane library were searched from inception of the databases until December 2021. We included placebo-controlled RCTs of adult patients with UC treated with aminosalicylates, corticosteroids, immunosuppressives, biologics, and small molecules. We pooled estimates using a random-effects model and performed subgroup analysis and meta-regression to evaluate the effect of different covariates on placebo rates.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Thirty-three studies (30 induction and 3 maintenance) were included. The overall placebo histological remission rate was 15.7% (95% confidence interval, 12.9%-19%) across all 33 studies. High heterogeneity was observed among studies with I2 = 62.10%. The pooled estimate of histological remission was 15.8% in induction studies and 14.5% in maintenance studies. Subgroup analysis revealed statistically significant differences in placebo rates when accounting for background medications, the intervention drug class, and disease severity (P = .041, .025, and .025, respectively). There was no statistical difference between induction vs maintenance studies or between different histological scales (P = .771, and .075, respectively).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Placebo histological remission rates range from 13% to 19% in UC RCTs, but studies are highly heterogeneous. Factors found to influence placebo rates include presence of background medications, the drug used, and the disease severity. These observations inform future trial designs to minimize placebo rates and reduce heterogeneity.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ibd\/izad013","type":"journal-article","created":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T18:34:15Z","timestamp":1675881255000},"page":"125-131","source":"Crossref","is-referenced-by-count":1,"title":["Histological Remission Placebo Rates in Ulcerative Colitis Trials: A Systematic Review and Meta-analysis"],"prefix":"10.1093","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8463-6601","authenticated-orcid":false,"given":"Michael","family":"Youssef","sequence":"first","affiliation":[{"name":"Faculty of Medicine, University of Toronto , Toronto, ON , Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelly","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of General Surgery, McMaster University , Hamilton, ON , Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"So Jeong","family":"Lee","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Toronto , Toronto, ON , Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neeraj","family":"Narula","sequence":"additional","affiliation":[{"name":"Department of Medicine (Division of Gastroenterology) and Farncombe Family Digestive Health Research Institute, McMaster University , Hamilton ON , Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,2,8]]},"reference":[{"key":"2024021916265000700_CIT0001","doi-asserted-by":"crossref","first-page":"1756284819853201756284819853208","DOI":"10.1177\/1756284819853208","article-title":"New biologics and small molecules in inflammatory bowel disease: an update","volume":"12","author":"Sabino","year":"2019","journal-title":"Ther Adv 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Is \u2018complete\u2019 remission the new treatment paradigm? An IOIBD initiative","volume":"8","author":"Bryant","year":"2014  1","journal-title":"J Crohn\u2019s Colitis"},{"issue":"11","key":"2024021916265000700_CIT0013","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1136\/gutjnl-2014-307536","article-title":"Reproducibility of histological assessments of disease activity in UC","volume":"64","author":"Mosli","year":"2015  1","journal-title":"Gut."},{"issue":"5","key":"2024021916265000700_CIT0014","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1136\/gutjnl-2021-326376","article-title":"PICaSSO Histologic Remission Index (PHRI) in ulcerative colitis: development of a novel simplified histological score for monitoring mucosal healing and predicting clinical outcomes and its applicability in an artificial intelligence system","volume":"71","author":"Gui","year":"2022  1","journal-title":"Gut."},{"key":"2024021916265000700_CIT0015","article-title":"Correspondence on \u201cPICaSSO Histologic Remission Index (PHRI) in ulcerative colitis: development of a novel simplified histological score for monitoring mucosal healing and predicting clinical outcomes and its applicability in an artificial intelligence system\u201d by Gui et al","author":"Wong","year":"2022  7","journal-title":"Gut."},{"issue":"11","key":"2024021916265000700_CIT0016","doi-asserted-by":"crossref","first-page":"2510","DOI":"10.1016\/j.cgh.2019.12.011","article-title":"Complete resolution of mucosal neutrophils associates with improved long-term clinical outcomes of patients with ulcerative colitis","volume":"18","author":"Pai","year":"2020  1","journal-title":"Clin Gastroenterol Hepatol."},{"issue":"1","key":"2024021916265000700_CIT0017","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1136\/gutjnl-2015-310187","article-title":"Development and validation of the Nancy histological index for UC","volume":"66","author":"Marchal-Bressenot","year":"2017  1","journal-title":"Gut."},{"issue":"5","key":"2024021916265000700_CIT0018","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1080\/00365521.2021.1897670","article-title":"Increased use of biologics in the era of TNF-\u03b1 inhibitors did not reduce surgical rate but prolonged the time from diagnosis to first time intestinal resection among patients with Crohn\u2019s disease and ulcerative colitis\u2013a Danish register-based study from 2003\u20132016","volume":"56","author":"Qvist","year":"2021  4","journal-title":"Scand J Gastroenterol."}],"container-title":["Inflammatory Bowel Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ibdjournal\/advance-article-pdf\/doi\/10.1093\/ibd\/izad013\/49126859\/izad013.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ibdjournal\/article-pdf\/30\/1\/125\/56706911\/izad013.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ibdjournal\/article-pdf\/30\/1\/125\/56706911\/izad013.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,19]],"date-time":"2024-02-19T16:27:06Z","timestamp":1708360026000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ibdjournal\/article\/30\/1\/125\/7031700"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,8]]},"references-count":18,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,2,8]]},"published-print":{"date-parts":[[2024,1,5]]}},"URL":"https:\/\/doi.org\/10.1093\/ibd\/izad013","relation":{},"ISSN":["1078-0998","1536-4844"],"issn-type":[{"type":"print","value":"1078-0998"},{"type":"electronic","value":"1536-4844"}],"subject":[],"published-other":{"date-parts":[[2024,1,1]]},"published":{"date-parts":[[2023,2,8]]}}}