{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T13:00:51Z","timestamp":1789736451060,"version":"4.0.1"},"reference-count":21,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2022,7,26]],"date-time":"2022-07-26T00:00:00Z","timestamp":1658793600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Vivli","award":["#00006041"],"award-info":[{"award-number":["#00006041"]}]},{"DOI":"10.13039\/100006483","name":"Abbvie","doi-asserted-by":"publisher","award":["#00006041"],"award-info":[{"award-number":["#00006041"]}],"id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The terminal ileum poses a predilection for Crohn\u2019s disease (CD) but is less susceptible to undergo healing to treatment with biologics and small molecules. This study aimed to evaluate histologic features associated with endoscopic remission (ER).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This is a post hoc analysis of patients with moderately to severely active CD, defined as Crohn\u2019s disease activity index 220 to 450, and terminal ileal ulceration treated with antitumor necrosis factor (TNF)-\u03b1 inhibitor adalimumab from the EXTEND trial. We studied whether baseline total Global Histologic Disease Activity Scores (GHAS), any individual histologic element, and specific immunohistochemical (IHC) markers of chronic inflammation from biopsy specimens were associated with postinduction (week 12) and maintenance (week 52) ER, defined as Simple Endoscopic Score for Crohn\u2019s Disease of 0. Multivariable logistic regression models adjusted for confounders were used to assess the relationship between histologic markers and 1-year outcomes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Seventy-one adult patients with CD affecting the ileum were included in this analysis. Both baseline ileal GHAS scores and individual histologic components were not found to be associated with ER at weeks 12 or 52. Increased expression of interleukin-13 receptor (IL-13R) on IHC stains was associated with reduced likelihood of achieving 1-year ER (adjusted odds ratio, 0.06; 95% CI, 0.01-0.92; P = .044). No other biomarker assessed was associated with 1-year ER.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Ileal histologic disease activity and IHC activation markers of chronic mucosal inflammation were not associated with 1-year ER. However, strong staining for IL-13 receptor in the ileum was associated with reduced odds of 1-year ER using adalimumab. Mucosal cellular disease profiles might pose an opportunity to guide treatment of CD.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ibd\/izac157","type":"journal-article","created":{"date-parts":[[2022,7,26]],"date-time":"2022-07-26T10:58:48Z","timestamp":1658833128000},"page":"875-882","source":"Crossref","is-referenced-by-count":3,"title":["Increased Expression of Interleukin-13 Receptor in Ileum Associated With Nonresponse to Adalimumab in Ileal Crohn\u2019s Disease"],"prefix":"10.1093","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9472-201X","authenticated-orcid":false,"given":"Emily C L","family":"Wong","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Gastroenterology, and Farncombe Family Digestive Health Research Institute; McMaster University , Hamilton ON , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arif","family":"Yusuf","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Gastroenterology, and Farncombe Family Digestive Health Research Institute; McMaster University , Hamilton ON , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jagoda","family":"Pokryszka","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna , W\u00e4hringer G\u00fcrtel 18-20, Vienna , Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9514-2321","authenticated-orcid":false,"given":"Parambir S","family":"Dulai","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Northwestern University , Chicago, IL , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6472-249X","authenticated-orcid":false,"given":"Jean-Frederic","family":"Colombel","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Icahn School of Medicine at Mount Sinai , New York, NY , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John K","family":"Marshall","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Gastroenterology, and Farncombe Family Digestive Health Research Institute; McMaster University , Hamilton ON , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Reinisch","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna , W\u00e4hringer G\u00fcrtel 18-20, Vienna , Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1536-8436","authenticated-orcid":false,"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":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,7,26]]},"reference":[{"issue":"9","key":"2023060109575629000_CIT0001","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1038\/ajg.2015.233","article-title":"Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): determining therapeutic goals for treat-to-target","volume":"110","author":"Peyrin-Biroulet","year":"2015","journal-title":"Am J Gastroenterol."},{"issue":"5","key":"2023060109575629000_CIT0002","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1053\/j.gastro.2020.12.031","article-title":"STRIDE-II: an update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): determining therapeutic goals for treat-to-target strategies in IBD","volume":"160","author":"Turner","year":"2021","journal-title":"Gastroenterology."},{"issue":"12","key":"2023060109575629000_CIT0003","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1016\/j.crohns.2014.08.011","article-title":"Systematic review: histological remission in inflammatory bowel disease. Is \u201ccomplete\u201d remission the new treatment paradigm? An IOIBD initiative","volume":"8","author":"Bryant","year":"2014","journal-title":"J Crohns Colitis."},{"issue":"11","key":"2023060109575629000_CIT0004","doi-asserted-by":"crossref","first-page":"2518","DOI":"10.1016\/j.cgh.2019.11.056","article-title":"Histologic healing is more strongly associated with clinical outcomes in ileal Crohn\u2019s disease than endoscopic healing","volume":"18","author":"Christensen","year":"2020","journal-title":"Clin Gastroenterol Hepatol."},{"issue":"9","key":"2023060109575629000_CIT0005","doi-asserted-by":"crossref","first-page":"1800","DOI":"10.1016\/j.cgh.2020.09.046","article-title":"Treat to target: the role of histologic healing in inflammatory bowel diseases, a systematic review and meta-analysis","volume":"19","author":"Gupta","year":"2021","journal-title":"Clin Gastroenterol Hepatol."},{"issue":"1","key":"2023060109575629000_CIT0006","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1097\/MIB.0000000000000202","article-title":"Role for therapeutic drug monitoring during induction therapy with TNF antagonists in IBD: evolution in the definition and management of primary nonresponse","volume":"21","author":"Papamichael","year":"2015","journal-title":"Inflamm Bowel Dis."},{"issue":"8","key":"2023060109575629000_CIT0007","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.14309\/ajg.0000000000000617","article-title":"Ileal and rectal ulcer size affects the ability to achieve endoscopic remission: a post hoc analysis of the SONIC trial","volume":"115","author":"Narula","year":"2020","journal-title":"Am J Gastroenterol."},{"issue":"4","key":"2023060109575629000_CIT0008","first-page":"425","article-title":"Characterisation of mucosal healing with adalimumab treatment in patients with moderately to severely active Crohn\u2019s disease: results from the EXTEND trial","volume":"11","author":"Reinisch","year":"2017","journal-title":"J Crohns Colitis."},{"key":"2023060109575629000_CIT0009","doi-asserted-by":"crossref","first-page":"1756284820976923","DOI":"10.1177\/1756284820976923","article-title":"Efficacy of infliximab treatment on the mucosal healing of different intestinal segments in patients with ileocolonic Crohn\u2019s disease","volume":"13","author":"Wu","year":"2020","journal-title":"Therap Adv Gastroenterol."},{"issue":"1","key":"2023060109575629000_CIT0010","doi-asserted-by":"crossref","first-page":"134","DOI":"10.14309\/ajg.0000000000000834","article-title":"Location but Not Severity of Endoscopic Lesions Influences Endoscopic Remission Rates in Crohn\u2019s Disease: A Post Hoc Analysis of TAILORIX","volume":"116","author":"Rivi\u00e8re","year":"2021","journal-title":"Am J Gastroenterol."},{"issue":"5","key":"2023060109575629000_CIT0011","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1053\/j.gastro.2012.01.035","article-title":"Adalimumab induces and maintains mucosal healing in patients with Crohn\u2019s disease: data from the EXTEND trial","volume":"142","author":"Rutgeerts","year":"2012","journal-title":"Gastroenterology."},{"issue":"4","key":"2023060109575629000_CIT0012","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/S0016-5107(04)01878-4","article-title":"Development and validation of a new, simplified endoscopic activity score for Crohn\u2019s disease: the SES-CD","volume":"60","author":"Daperno","year":"2004","journal-title":"Gastrointest Endosc."},{"issue":"5","key":"2023060109575629000_CIT0013","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1016\/S0016-5085(99)70005-3","article-title":"Endoscopic and histological healing with infliximab anti-tumor necrosis factor antibodies in Crohn\u2019s disease: a European multicenter trial","volume":"116","author":"D\u2019Haens","year":"1999","journal-title":"Gastroenterology."},{"issue":"10014","key":"2023060109575629000_CIT0014","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/S0140-6736(15)00465-1","article-title":"Inherited determinants of Crohn\u2019s disease and ulcerative colitis phenotypes: a genetic association study","volume":"387","author":"Cleynen","year":"2016","journal-title":"Lancet."},{"issue":"4","key":"2023060109575629000_CIT0015","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1097\/MIB.0000000000000674","article-title":"Microbiome heterogeneity characterizing intestinal tissue and inflammatory bowel disease phenotype","volume":"22","author":"Tyler","year":"2016","journal-title":"Inflamm Bowel Dis."},{"issue":"2","key":"2023060109575629000_CIT0016","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1136\/gutjnl-2014-307916","article-title":"Compartment-specific immunity in the human gut: properties and functions of dendritic cells in the colon versus the ileum","volume":"65","author":"Mann","year":"2016","journal-title":"Gut."},{"issue":"7","key":"2023060109575629000_CIT0017","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.1053\/j.gastro.2021.02.035","article-title":"An international consensus to standardize integration of histopathology in ulcerative colitis clinical trials","volume":"160","author":"Ma","year":"2021","journal-title":"Gastroenterology."},{"issue":"5","key":"2023060109575629000_CIT0018","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1111\/apt.15126","article-title":"Mucosal IL-13RA2 expression predicts nonresponse to anti-TNF therapy in Crohn\u2019s disease","volume":"49","author":"Verstockt","year":"2019","journal-title":"Aliment Pharmacol Ther."},{"key":"2023060109575629000_CIT0019","doi-asserted-by":"crossref","first-page":"2983","DOI":"10.3389\/fimmu.2018.02983","article-title":"Effects of epithelial IL-13R\u03b12 expression in inflammatory bowel disease","volume":"9","author":"Verstockt","year":"2018","journal-title":"Front Immunol."},{"issue":"6","key":"2023060109575629000_CIT0020","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1053\/j.gastro.2008.08.055","article-title":"IL-13 signaling via IL-13R alpha2 induces major downstream fibrogenic factors mediating fibrosis in chronic TNBS colitis","volume":"135","author":"Fichtner-Feigl","year":"2008","journal-title":"Gastroenterology."},{"issue":"9","key":"2023060109575629000_CIT0021","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.3390\/genes12091438","article-title":"Machine learning modeling from omics data as prospective tool for improvement of inflammatory bowel disease diagnosis and clinical classifications","volume":"12","author":"Stankovic","year":"2021","journal-title":"Genes (Basel)."}],"container-title":["Inflammatory Bowel Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ibdjournal\/advance-article-pdf\/doi\/10.1093\/ibd\/izac157\/45067727\/izac157.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ibdjournal\/article-pdf\/29\/6\/875\/50463341\/izac157.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ibdjournal\/article-pdf\/29\/6\/875\/50463341\/izac157.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T09:59:16Z","timestamp":1685613556000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ibdjournal\/article\/29\/6\/875\/6650010"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,26]]},"references-count":21,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,7,26]]},"published-print":{"date-parts":[[2023,6,1]]}},"URL":"https:\/\/doi.org\/10.1093\/ibd\/izac157","relation":{},"ISSN":["1078-0998","1536-4844"],"issn-type":[{"value":"1078-0998","type":"print"},{"value":"1536-4844","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,6,1]]},"published":{"date-parts":[[2022,7,26]]}}}