{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T09:49:33Z","timestamp":1791625773631,"version":"4.3.4"},"reference-count":56,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T00:00:00Z","timestamp":1731542400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T00:00:00Z","timestamp":1731542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>High placebo responses have limited drug development in eosinophilic oesophagitis. The optimal configuration of trial outcomes is uncertain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To inform more efficient future trial designs, to characterise clinical, endoscopic and histologic placebo responses in eosinophilic oesophagitis randomised controlled trials (RCTs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We updated a Cochrane systematic review and meta\u2010analysis, searching multiple databases to January 1, 2024, to identify placebo\u2010controlled RCTs evaluating medical therapies for patients with eosinophilic oesophagitis. The primary outcome was the pooled proportion of study\u2010defined clinical, endoscopic and histologic responders and remitters randomised to placebo, using an intention\u2010to\u2010treat approach and random\u2010effects model. Sources of heterogeneity were explored using meta\u2010regression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We included 25 RCTs. The pooled proportion of clinical response was 41.0% [95% CI: 29.7%\u201352.8%] with substantial heterogeneity (\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u200974.9%). On meta\u2010regression, older age and a higher probability of being randomised to placebo reduced the likelihood of clinical response to placebo. The pooled proportion of histologic remission defined as a peak eosinophil count [PEC]\u2009\u2264\u20096 eosinophils per high power field [HPF] or\u2009\u2264\u20091 eosinophil\/HPF was 4.3% [95% CI: 2.6%\u20136.2%] (\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u200923.6%) and 1.3% [95% CI: 0.5%\u20132.5%] (\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090%), respectively. The standardised mean difference in the Eosinophilic Oesophagitis Endoscopic Reference Score to placebo was \u22120.25 [95% CI: \u22120.41, \u22120.10].\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Over 40% of patients in eosinophilic oesophagitis trials respond clinically to placebo, and this is associated with trial design factors such as randomisation ratio and trial population. Objective endoscopic and histologic measures are associated with very low placebo responses.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apt.18382","type":"journal-article","created":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T01:59:24Z","timestamp":1731635964000},"page":"32-43","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Meta\u2010Analysis: Evaluating Placebo Rates Across Outcomes in Eosinophilic Oesophagitis Randomised Controlled Trials"],"prefix":"10.1111","volume":"61","author":[{"given":"Angelica","family":"Rivas","sequence":"first","affiliation":[{"name":"Department of Medicine University of Calgary  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Newaz Shubidito","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Calgary  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhong","family":"Yuan","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology London Health Science Centre  London Ontario Canada"},{"name":"Department of Medicine Western University  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anila","family":"Qasim","sequence":"additional","affiliation":[{"name":"Alimentiv Inc  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B.","family":"O'Gorman","sequence":"additional","affiliation":[{"name":"Alimentiv Inc  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian G.","family":"Feagan","sequence":"additional","affiliation":[{"name":"Department of Medicine Western University  London Ontario Canada"},{"name":"Alimentiv Inc  London Ontario Canada"},{"name":"Department of Epidemiology and Biostatistics Western University  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1092-0033","authenticated-orcid":false,"given":"Vipul","family":"Jairath","sequence":"additional","affiliation":[{"name":"Department of Medicine Western University  London Ontario Canada"},{"name":"Alimentiv Inc  London Ontario Canada"},{"name":"Department of Epidemiology and Biostatistics Western University  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert J.","family":"Bredenoord","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Amsterdam University Medical Center  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan S.","family":"Dellon","sequence":"additional","affiliation":[{"name":"Center for Esophageal Diseases and Swallowing, and Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology University of North Carolina School of Medicine  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4698-9948","authenticated-orcid":false,"given":"Christopher","family":"Ma","sequence":"additional","affiliation":[{"name":"Alimentiv Inc  London Ontario Canada"},{"name":"Division of Gastroenterology &amp; Hepatology, Departments of Medicine and Community Health Sciences University of Calgary  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2018.07.009"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.815842"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2023.06.005"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2021.14920"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/17562848211068665"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2022-327326"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.02.038"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/2050640616689525"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2024.02.020"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2022.09.027"},{"key":"e_1_2_7_12_1","unstructured":"US Food and Drug Administration \u201cEosinophilic Esophagitis: Developing Drugs for Treatment. 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