{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:18:25Z","timestamp":1783383505986,"version":"3.54.6"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"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":[[2026,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The optimal timing for initiating immunomodulators (IMs) in Crohns disease (CD) remains unclear. We assessed whether early IM therapy reduces the risk of intestinal resection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>MEDLINE, EMBASE, and the Cochrane Library were systematically searched for studies comparing outcomes by timing of IM (thiopurines or methotrexate) initiation in CD. The primary outcome was intestinal resection. Pooled hazard ratios (HRs) with 95% CIs were calculated using a random-effects model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Seven cohort studies including 4297 patients were analyzed. Early IM initiation was associated with a 47% lower risk of intestinal resection compared with late or no IM therapy (pooled HR, 0.53; 95% CI, 0.44-0.65; I2 = 23%). This protective effect was consistent across subgroups, including studies in which all patients received IMs and early initiation was associated with a lower risk than late initiation (HR 0.59; 95% CI, 0.42-0.83). When early treatment was defined as initiation within 1-2\u2009years of diagnosis, early IM use was associated with a lower risk of intestinal resection than late or no IM therapy, with no heterogeneity (HR 0.55; 95% CI, 0.43-0.70; I2 = 0%). A broader definition of early treatment as within 3\u2009years of diagnosis also showed benefit compared with late or no IM therapy (HR, 0.52; 95% CI, 0.37-0.74) but with moderate heterogeneity (I2 = 57%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Early IM therapy is associated with a substantially lower risk of intestinal resection in CD compared with later or no IM therapy. The most consistent benefit occurs when treatment is initiated within the first 1-2\u2009years after diagnosis, supporting the concept of a therapeutic \u201cwindow of opportunity\u201d during which timely IM initiation may favorably alter the disease course.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ibd\/izag040","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T12:19:26Z","timestamp":1773058766000},"page":"1333-1343","source":"Crossref","is-referenced-by-count":0,"title":["Early immunomodulator therapy reduces the risk of intestinal resection in Crohns disease: a systematic review and meta-analysis"],"prefix":"10.1093","volume":"32","author":[{"given":"Jiyoung","family":"Yoon","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine, Kangdong Sacred Heart Hospital , Seoul,","place":["South Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu Kyung","family":"Jun","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Bundang Hospital , Seongnam,","place":["South Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6328-6948","authenticated-orcid":false,"given":"Hye Sun","family":"Lee","sequence":"additional","affiliation":[{"name":"Biostatics Collaboration Unit, Yonsei University College of Medicine , Seoul,","place":["Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun Hwan","family":"Yoo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, CHA Bundang Medical Center, CHA University School of Medicine , Seongnam,","place":["South Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5297-5414","authenticated-orcid":false,"given":"Jae Jun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine , Seoul,","place":["Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,4,13]]},"reference":[{"key":"2026070620112436400_izag040-B1","doi-asserted-by":"publisher","first-page":"1741","DOI":"10.1016\/S0140-6736(16)31711-1","article-title":"Crohn\u2019s disease","volume":"389","author":"Torres","year":"2017","journal-title":"Lancet"},{"key":"2026070620112436400_izag040-B2","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1097\/00000658-200001000-00006","article-title":"Risk factors for surgery and postoperative recurrence in Crohn\u2019s disease","volume":"231","author":"Bernell","year":"2000","journal-title":"Ann Surg"},{"key":"2026070620112436400_izag040-B3","doi-asserted-by":"publisher","first-page":"2179","DOI":"10.1136\/gutjnl-2017-314519","article-title":"Early intervention in Crohn\u2019s disease: towards disease modification trials","volume":"66","author":"Danese","year":"2017","journal-title":"Gut"},{"key":"2026070620112436400_izag040-B4","first-page":"CD000545","article-title":"Azathioprine or 6-mercaptopurine for maintenance of remission in Crohn\u2019s disease","author":"Prefontaine","year":"2010","journal-title":"Cochrane Database Syst Rev"},{"key":"2026070620112436400_izag040-B5","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1136\/gut.2004.045294","article-title":"Impact of the increasing use of immunosuppressants in Crohn\u2019s disease on the need for intestinal surgery","volume":"54","author":"Cosnes","year":"2005","journal-title":"Gut"},{"key":"2026070620112436400_izag040-B6","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1038\/ajg.2013.462","article-title":"The impact of timing and duration of thiopurine treatment on first intestinal resection in Crohn\u2019s disease: national UK population-based study 1989-2010","volume":"109","author":"Chatu","year":"2014","journal-title":"Am J Gastroenterol"},{"key":"2026070620112436400_izag040-B7","doi-asserted-by":"publisher","first-page":"990","DOI":"10.1111\/apt.13361","article-title":"Impact of early thiopurines on surgery in 2770 children and young people diagnosed with inflammatory bowel disease: a national population-based study","volume":"42","author":"Chhaya","year":"2015","journal-title":"Aliment Pharmacol Ther"},{"key":"2026070620112436400_izag040-B8","doi-asserted-by":"publisher","first-page":"1206","DOI":"10.1038\/s41395-018-0108-6","article-title":"Persistence with immunomodulator monotherapy use and incidence of therapeutic ineffectiveness among users of immunomodulator monotherapy in IBD","volume":"113","author":"Targownik","year":"2018","journal-title":"Am J Gastroenterol"},{"key":"2026070620112436400_izag040-B9","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1053\/j.gastro.2013.04.048","article-title":"Early administration of azathioprine vs conventional management of Crohn\u2019s Disease: a randomized controlled trial","volume":"145","author":"Cosnes","year":"2013","journal-title":"Gastroenterology"},{"key":"2026070620112436400_izag040-B10","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1053\/j.gastro.2013.06.009","article-title":"Early azathioprine therapy is no more effective than placebo for newly diagnosed Crohn\u2019s disease","volume":"145","author":"Pan\u00e9s","year":"2013","journal-title":"Gastroenterology"},{"key":"2026070620112436400_izag040-B11","doi-asserted-by":"publisher","first-page":"249","DOI":"10.4082\/kjfm.23.0034","article-title":"RoBANS 2: a revised risk of bias assessment tool for nonrandomized studies of interventions","volume":"44","author":"Seo","year":"2023","journal-title":"Korean J Fam Med"},{"key":"2026070620112436400_izag040-B12","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1556\/OH.2012.29331","volume":"153","author":"Golovics","year":"2012","journal-title":"Orv Hetil"},{"key":"2026070620112436400_izag040-B13","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1093\/ecco-jcc\/jjw146","article-title":"Clinical characteristics and long-term outcomes of paediatric Crohn\u2019s disease: a single-centre experience","volume":"11","author":"Kim","year":"2017","journal-title":"J Crohns Colitis"},{"key":"2026070620112436400_izag040-B14","doi-asserted-by":"publisher","first-page":"1382","DOI":"10.1097\/MIB.0000000000000119","article-title":"Early use of thiopurines or methotrexate reduces major abdominal and perianal surgery in Crohn\u2019s disease","volume":"20","author":"Kariyawasam","year":"2014","journal-title":"Inflamm Bowel Dis"},{"key":"2026070620112436400_izag040-B15","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1111\/apt.13363","article-title":"Impact of the early use of immunomodulators or TNF antagonists on bowel damage and surgery in Crohn\u2019s disease","volume":"42","author":"Safroneeva","year":"2015","journal-title":"Aliment Pharmacol Ther"},{"key":"2026070620112436400_izag040-B16","doi-asserted-by":"publisher","first-page":"1200","DOI":"10.1136\/gut.2009.202101","article-title":"Natural history of Crohn\u2019s disease in a population-based cohort from Cardiff (1986-2003): a study of changes in medical treatment and surgical resection rates","volume":"59","author":"Ramadas","year":"2010","journal-title":"Gut"},{"key":"2026070620112436400_izag040-B17","doi-asserted-by":"publisher","first-page":"Cd006884","DOI":"10.1002\/14651858.CD006884.pub3","article-title":"Methotrexate for maintenance of remission in Crohn\u2019s disease","volume":"2014","author":"Patel","year":"2014","journal-title":"Cochrane Database Syst Rev"},{"key":"2026070620112436400_izag040-B18","doi-asserted-by":"publisher","first-page":"1383","DOI":"10.1056\/NEJMoa0904492","article-title":"Infliximab, azathioprine, or combination therapy for Crohn\u2019s disease","volume":"362","author":"Colombel","year":"2010","journal-title":"N Engl J Med"},{"key":"2026070620112436400_izag040-B19","doi-asserted-by":"publisher","first-page":"1259","DOI":"10.1093\/ecco-jcc\/jjw152","article-title":"Adalimumab monotherapy and a combination with azathioprine for Crohn\u2019s disease: a prospective, randomized trial","volume":"10","author":"Matsumoto","year":"2016","journal-title":"J Crohns Colitis"},{"key":"2026070620112436400_izag040-B20","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.1111\/apt.13808","article-title":"Adalimumab or infliximab as monotherapy, or in combination with an immunomodulator, in the treatment of Crohn\u2019s disease","volume":"44","author":"Cosnes","year":"2016","journal-title":"Aliment Pharmacol Ther"},{"key":"2026070620112436400_izag040-B21","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1586\/17474124.2015.1039987","article-title":"Toxicity and response to thiopurines in patients with inflammatory bowel disease","volume":"9","author":"Goldberg","year":"2015","journal-title":"Expert Rev Gastroenterol Hepatol"},{"key":"2026070620112436400_izag040-B22","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1016\/j.cgh.2014.05.015","article-title":"Risk of lymphoma in patients with inflammatory bowel disease treated with azathioprine and 6-mercaptopurine: a meta-analysis","volume":"13","author":"Kotlyar","year":"2015","journal-title":"Clin Gastroenterol Hepatol"},{"key":"2026070620112436400_izag040-B23","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1093\/ecco-jcc\/jjad135","article-title":"Thiopurines have sustained long-term effectiveness in patients with inflammatory bowel disease, which is independent of disease duration at initiation: a propensity score matched analysis","volume":"18","author":"Ranjan","year":"2024","journal-title":"J Crohns Colitis"},{"key":"2026070620112436400_izag040-B24","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1136\/gutjnl-2019-320185","article-title":"Thiopurine monotherapy is effective in ulcerative colitis but significantly less so in Crohn\u2019s disease: long-term outcomes for 11\u2009928 patients in the UK inflammatory bowel disease bioresource","volume":"70","author":"Stournaras","year":"2021","journal-title":"Gut"}],"container-title":["Inflammatory Bowel Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ibdjournal\/article-pdf\/32\/7\/1333\/68070849\/izag040.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ibdjournal\/article-pdf\/32\/7\/1333\/68070849\/izag040.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:11:29Z","timestamp":1783383089000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ibdjournal\/article\/32\/7\/1333\/8653296"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,13]]},"references-count":24,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,4,13]]},"published-print":{"date-parts":[[2026,7,1]]}},"URL":"https:\/\/doi.org\/10.1093\/ibd\/izag040","relation":{},"ISSN":["1078-0998","1536-4844"],"issn-type":[{"value":"1078-0998","type":"print"},{"value":"1536-4844","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,7]]},"published":{"date-parts":[[2026,4,13]]}}}