{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T10:01:15Z","timestamp":1792144875413,"version":"4.4.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T00:00:00Z","timestamp":1726099200000},"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":[[2025,3,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Criteria for \u201cdifficult-to-treat\u201d inflammatory bowel disease (DTT-IBD) have recently been proposed to standardize terminology. We aimed to evaluate the prevalence, characteristics, management, and outcomes of DTT-IBD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective study in 2 tertiary centers in Italy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 1736 IBD patients treated with biologics\/advanced small molecules, 430 (24.8%) met at least 1 DTT-IBD criterion, of which 331 (77%) failed at least 2 mechanisms of action. In ulcerative colitis (UC), left-sided and extended colitis were risk factors for DTT compared to proctitis (odds ratio [OR] 6.55; 95% confidence interval [CI], 1.93-40.98; p\u2005=\u20050.011 and OR 10.12; 95% CI, 3.01-63.14; p\u2005=\u20050.002, respectively). In Crohn\u2019s disease (CD), multiple localizations (L3+L4) (OR 3.04; 95% CI, 1.09-8.34; p\u2005=\u20050.03), stricturing (OR 2.24; 95% CI, 1.52-3.34; p\u2005&amp;lt;\u20050.001), and penetrating (OR 2.33; 95% CI, 1.55-3.53; p\u2005&amp;lt;\u20050.001) behaviors, and perianal disease (OR 2.49; 95% CI, 1.75-3.53; p\u2005&amp;lt;\u20050.001) were the main risk factors for DTT. Delay in advanced treatment initiation was positively associated with DTT-CD (OR 1.74; 95% CI, 1.27-2.41; p\u2005=\u20050.001) but protective in UC (OR 0.65; 95% CI, 0.45-0.93; p\u2005=\u20050.019). The rates of symptomatic, biochemical, and endoscopic remission were lower in DTT-IBD compared to non-DTT-IBD. The difference was most evident for endoscopic remission (25% vs 62%). Drug persistency in each following line of treatment progressively decreased in CD and UC. All advanced drugs used in DTT-IBD had similar persistence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>DTT-IBD was prevalent in approximately one-quarter of patients with IBD in a tertiary care setting. Certain IBD phenotypes and the delay in initiating treatment in CD were risk factors for DTT. Drug persistency decreased progressively with every subsequent line of therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ecco-jcc\/jjae145","type":"journal-article","created":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T11:54:11Z","timestamp":1726055651000},"source":"Crossref","is-referenced-by-count":29,"title":["Prevalence, Characteristics, Management, and Outcomes of Difficult-to-Treat Inflammatory Bowel Disease"],"prefix":"10.1093","volume":"19","author":[{"given":"Tommaso Lorenzo","family":"Parigi","sequence":"first","affiliation":[{"name":"IBD Unit, Department of Gastroenterology, IRCCS Ospedale San Raffaele , Milan ,","place":["Italy"]},{"name":"Division of Immunology, Transplantation and Infectious Disease, University Vita-Salute San Raffaele , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Massimino","sequence":"additional","affiliation":[{"name":"IBD Unit, Department of Gastroenterology, 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Raffaele , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Bezzio","sequence":"additional","affiliation":[{"name":"IBD Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital , Milan ,","place":["Italy"]},{"name":"Department of Biomedical Sciences, Humanitas University , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8543-4355","authenticated-orcid":false,"given":"Arianna","family":"Dal Buono","sequence":"additional","affiliation":[{"name":"IBD Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferdinando","family":"D\u2019Amico","sequence":"additional","affiliation":[{"name":"IBD Unit, Department of Gastroenterology, IRCCS Ospedale San Raffaele , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Furfaro","sequence":"additional","affiliation":[{"name":"IBD Unit, Department of Gastroenterology, IRCCS Ospedale San Raffaele , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Loy","sequence":"additional","affiliation":[{"name":"IBD Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Zilli","sequence":"additional","affiliation":[{"name":"IBD Unit, Department of Gastroenterology, IRCCS Ospedale San Raffaele , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Ungaro","sequence":"additional","affiliation":[{"name":"IBD Unit, Department of Gastroenterology, IRCCS Ospedale San Raffaele , Milan 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