{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T04:31:26Z","timestamp":1762749086294,"version":"build-2065373602"},"reference-count":0,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"am","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Placebo response rates in ulcerative colitis (UC) trials are highly variable. It is uncertain whether adding objective measures of inflammation, such as fecal calprotectin (FC) or histologic activity, to conventional eligibility criteria could reduce placebo response and strengthen treatment effect estimates. This study evaluated whether applying baseline FC or histology thresholds would alter outcomes in UC clinical trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a post-hoc pooled analysis of individual patient-level data from five phase 3, randomized, placebo-controlled trials including 1,918 patients on active therapy and 1,149 on placebo. Baseline FC thresholds (&amp;gt;150, &amp;gt;200, &amp;gt;250, &amp;gt;500\u2009\u00b5g\/g) and Geboes histological thresholds (\u22653.1, \u22653.2) were applied as hypothetical inclusion criteria. Outcomes assessed were post-induction clinical remission (CR: modified Mayo score with stool frequency \u22641 and \u22651-point decrease, rectal bleeding\u2009=\u20090, and endoscopic subscore \u22641) and endoscopic improvement (EI: endoscopic subscore \u22641).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Applying FC or Geboes thresholds did not meaningfully reduce placebo response rates or increase treatment-placebo differences for CR or EI. For example, in vedolizumab, the CR difference versus placebo was 11% (95% CI: 3.5-18.5) in the unrestricted population and 10.4\u201313% with thresholds applied, with up to 91 (33.6%) of participants excluded. For upadacitinib, EI differences were 36.2% (95% CI: 28.5-43.8) unrestricted and 35.9\u201337.3% with restrictions, with up to 248 (38.7%) of participants excluded. Results were consistent across therapies and in subgroup analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Restricting trial enrollment based on elevated FC or histological activity did not meaningfully lower placebo response rates in phase 3 UC trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ecco-jcc\/jjaf194","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T13:04:28Z","timestamp":1762520668000},"source":"Crossref","is-referenced-by-count":0,"title":["Addition of Baseline Histology and Fecal Calprotectin Does Not Reduce Placebo Rates in Ulcerative Colitis Clinical Trials: Post-hoc Analysis of Patient Level Data"],"prefix":"10.1093","author":[{"given":"Emily C L","family":"Wong","sequence":"first","affiliation":[{"name":"McMaster University Department of Medicine (Division of Gastroenterology) and Farncombe Family Digestive Health Research Institute, , Hamilton, ON,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John K","family":"Marshall","sequence":"additional","affiliation":[{"name":"McMaster University Department of Medicine (Division of Gastroenterology) and Farncombe Family Digestive Health Research Institute, , Hamilton, ON,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Ma","sequence":"additional","affiliation":[{"name":"University of Calgary Department of Medicine, Division of Gastroenterology, Cumming School of Medicine, , Calgary, ON,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vipul","family":"Jairath","sequence":"additional","affiliation":[{"name":"Western University Department of Medicine, Division of Gastroenterology, , London, ON,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Parambir S","family":"Dulai","sequence":"additional","affiliation":[{"name":"Northwestern University Division of Gastroenterology, , Chicago, IL,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Walter","family":"Reinisch","sequence":"additional","affiliation":[{"name":"Medical University of Vienna Department of Internal Medicine III, Division of Gastroenterology and Hepatology, , W\u00e4hringer G\u00fcrtel 18-20, Vienna,","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neeraj","family":"Narula","sequence":"additional","affiliation":[{"name":"McMaster University Department of Medicine (Division of Gastroenterology) and Farncombe Family Digestive Health Research Institute, , Hamilton, ON,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,11,9]]},"container-title":["Journal of Crohn's and Colitis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ecco-jcc\/advance-article-pdf\/doi\/10.1093\/ecco-jcc\/jjaf194\/65249650\/jjaf194.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ecco-jcc\/advance-article-pdf\/doi\/10.1093\/ecco-jcc\/jjaf194\/65249650\/jjaf194.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T04:26:36Z","timestamp":1762748796000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ecco-jcc\/advance-article\/doi\/10.1093\/ecco-jcc\/jjaf194\/8317546"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,9]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1093\/ecco-jcc\/jjaf194","relation":{},"ISSN":["1873-9946","1876-4479"],"issn-type":[{"type":"print","value":"1873-9946"},{"type":"electronic","value":"1876-4479"}],"subject":[],"published":{"date-parts":[[2025,11,9]]},"article-number":"jjaf194"}}