{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T04:32:51Z","timestamp":1775190771707,"version":"3.50.1"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T00:00:00Z","timestamp":1744243200000},"content-version":"vor","delay-in-days":9,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Antitumor necrosis factor (TNF) dose escalation is performed to improve therapeutic response and optimize outcomes in patients with Crohn\u2019s disease (CD). We aimed to describe the durability of anti-TNF therapy in patients with CD receiving escalated anti-TNF therapy, along with the overall durability of anti-TNF treatment between patients managed with a proactive versus reactive therapeutic drug monitoring (TDM) approach.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We undertook a retrospective multicentre cohort study. One center practiced proactive TDM with a weekly virtual TDM clinic, while the other practiced reactive TDM. Patients receiving escalated infliximab or adalimumab therapy for CD from January 2015 to April 2022 were included. Durability was defined as the time from biologic start to cessation for treatment failure.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>239 patients (45% female, median age 39) meeting criteria for inclusion were identified; 165 patients were included in the proactive TDM cohort and 74 in the reactive TDM cohort.<\/jats:p>\n                  <jats:p>Anti-TNF na\u00efve patients had significantly higher durability of therapy when compared with the anti-TNF exposed patients for both overall durability (P\u2005=\u2005.045) and durability postescalation (P\u2005=\u2005.017). The proactive TDM cohort had significantly higher durability when compared with the reactive cohort for both overall durability (P\u2005=\u2005.001) and durability postescalation (P\u2005=\u2005.002).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This multicentre, retrospective cohort study illustrates the importance of dose escalation as a therapeutic strategy in IBD care. The durability of anti-TNF therapy is superior in anti-TNF na\u00efve compared to exposed patients and can be improved further by proactive TDM to guide dose optimization.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/crocol\/otaf028","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T10:56:02Z","timestamp":1744282562000},"source":"Crossref","is-referenced-by-count":1,"title":["The Durability of Anti-TNF Therapy for Crohn\u2019s Disease Is Higher in Anti-TNF Na\u00efve Patients and Increases With Proactive Therapeutic Drug Monitoring"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6648-658X","authenticated-orcid":false,"given":"Robert","family":"Gilmore","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, St Vincent\u2019s Hospital , Melbourne ,","place":["Australia"]},{"name":"Department of Gastroenterology, Mater Hospital , Brisbane ,","place":["Australia"]},{"name":"Mater Research Institute, University of Queensland , South Brisbane ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Mater Hospital , Brisbane ,","place":["Australia"]},{"name":"Mater Research Institute, University of Queensland , South Brisbane ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamar","family":"Schildkraut","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, St Vincent\u2019s Hospital , Melbourne ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riddhi","family":"Joshi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, St Vincent\u2019s Hospital , Melbourne ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lyman","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, St Vincent\u2019s Hospital , Melbourne ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Vorgin","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Melbourne , Melbourne ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amirah","family":"Etchegaray","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Mater Hospital , Brisbane ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5977-3978","authenticated-orcid":false,"given":"Aathavan","family":"Shanmuga Anandan","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Mater Hospital , Brisbane ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Tambakis","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, St Vincent\u2019s Hospital , Melbourne ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moshe","family":"Loebenstein","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, St Vincent\u2019s Hospital , Melbourne ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoon-Kyo","family":"An","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Mater Hospital , Brisbane ,","place":["Australia"]},{"name":"Mater Research Institute, University of Queensland , South Brisbane ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5256-7672","authenticated-orcid":false,"given":"Jakob","family":"Begun","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Mater Hospital , Brisbane ,","place":["Australia"]},{"name":"Mater Research Institute, University of Queensland , South Brisbane ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3896-7826","authenticated-orcid":false,"given":"Emily K","family":"Wright","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, St Vincent\u2019s Hospital , Melbourne ,","place":["Australia"]},{"name":"Department of Medicine, University of Melbourne , Melbourne ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,4,9]]},"reference":[{"issue":"7","key":"2025070707413689900_CIT0001","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.1016\/j.mayocp.2017.04.010","article-title":"Crohn disease: epidemiology, diagnosis, and management","volume":"92","author":"Feuerstein","year":"2017","journal-title":"Mayo Clin Proc."},{"issue":"7","key":"2025070707413689900_CIT0002","doi-asserted-by":"publisher","first-page":"1072","DOI":"10.1136\/gutjnl-2012-304353","article-title":"Crohn\u2019s disease complicated by strictures: a systematic review","volume":"62","author":"Rieder","year":"2013","journal-title":"Gut."},{"issue":"6","key":"2025070707413689900_CIT0003","doi-asserted-by":"publisher","first-page":"1785","DOI":"10.1053\/j.gastro.2011.01.055","article-title":"Epidemiology and natural history of inflammatory bowel diseases","volume":"140","author":"Cosnes","year":"2011","journal-title":"Gastroenterology."},{"issue":"3","key":"2025070707413689900_CIT0004","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1111\/apt.16445","article-title":"Systematic review: societal cost of illness of inflammatory bowel disease is increasing due to biologics and varies between continents","volume":"54","author":"Van Linschoten","year":"2021","journal-title":"Alim Pharmacol Ther."},{"issue":"1","key":"2025070707413689900_CIT0005","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1093\/ecco-jcc\/jjab178","article-title":"ECCO guidelines on therapeutics in ulcerative colitis: medical treatment","volume":"16","author":"Raine","year":"2022","journal-title":"J Crohns Colitis."},{"issue":"5","key":"2025070707413689900_CIT0006","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1016\/S2468-1253(24)00034-7","article-title":"A biomarker-stratified comparison of top-down versus accelerated step-up treatment strategies for patients with newly diagnosed Crohn\u2019s disease (profile): a multicentre, open-label randomised controlled trial","volume":"9","author":"Noor","year":"2024","journal-title":"Lancet Gastroenterol Hepatol."},{"issue":"12","key":"2025070707413689900_CIT0007","doi-asserted-by":"publisher","first-page":"1896","DOI":"10.1093\/ibd\/izz059","article-title":"The role of early biologic therapy in inflammatory bowel disease","volume":"25","author":"Berg","year":"2019","journal-title":"Inflamm Bowel Dis."},{"issue":"7","key":"2025070707413689900_CIT0008","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1111\/apt.13353","article-title":"Efficacy of thiopurines and adalimumab in preventing Crohn\u2019s disease recurrence in high-risk patients \u2013 a POCER study analysis","volume":"42","author":"De Cruz","year":"2015","journal-title":"Alim. Pharmacol. Ther."},{"issue":"9317","key":"2025070707413689900_CIT0009","doi-asserted-by":"publisher","first-page":"1541-1549","DOI":"10.1016\/S0140-6736(02)08512-4","article-title":"Maintenance infliximab for Crohn\u2019s disease: The accent i randomised trial","volume":"359","author":"Hanauer","year":"2002","journal-title":"Lancet."},{"issue":"1","key":"2025070707413689900_CIT0010","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1053\/j.gastro.2006.11.041","article-title":"Adalimumab for maintenance of clinical response and remission in patients with Crohn\u2019s disease: the charm trial","volume":"132","author":"Colombel","year":"2007","journal-title":"Gastroenterology."},{"issue":"4","key":"2025070707413689900_CIT0011","doi-asserted-by":"publisher","first-page":"318-331","DOI":"10.1016\/S2468-1253(21)00393-9","article-title":"Intensive drug therapy versus standard drug therapy for symptomatic intestinal Crohn\u2019s disease strictures (strident): an open-label, single-centre, randomised controlled trial","volume":"7","author":"Schulberg","year":"2022","journal-title":"Lancet Gastroenterol. Hepatol."},{"issue":"12","key":"2025070707413689900_CIT0012","doi-asserted-by":"publisher","first-page":"2653","DOI":"10.3390\/jcm10122653","article-title":"Anti-drug antibodies in patients with inflammatory bowel diseases treated with biosimilar infliximab: a prospective cohort study","volume":"10","author":"P\u0119kala","year":"2021","journal-title":"J. Clin. Med."},{"issue":"1","key":"2025070707413689900_CIT0013","doi-asserted-by":"publisher","first-page":"1-7","DOI":"10.20524\/aog.2021.0682","article-title":"The efficacy of immunomodulators in the prevention and suppression of anti-drug antibodies to anti-tumor necrosis factor therapy in inflammatory bowel disease","volume":"35","author":"Fousekis","year":"2022","journal-title":"Ann. Gastroenterol."},{"issue":"5","key":"2025070707413689900_CIT0014","doi-asserted-by":"publisher","first-page":"2051","DOI":"10.1007\/s12325-023-02457-6","article-title":"Dose escalation patterns of advanced therapies in crohn\u2019s disease and ulcerative colitis: a systematic literature review","volume":"40","author":"Panaccione","year":"2023","journal-title":"Adv Ther."},{"issue":"7","key":"2025070707413689900_CIT0015","doi-asserted-by":"publisher","first-page":"933-940","DOI":"10.1111\/apt.13970","article-title":"Higher infliximab trough levels are associated with perianal fistula healing in patients with Crohn\u2019s disease","volume":"45","author":"Yarur","year":"2017","journal-title":"Alim. Pharmacol. Ther."},{"issue":"1","key":"2025070707413689900_CIT0016","doi-asserted-by":"publisher","first-page":"50-58","DOI":"10.1159\/000518755","article-title":"Proactive versus reactive therapeutic drug monitoring: why, when, and how","volume":"7","author":"Shmais","year":"2021","journal-title":"Inflamm. Bowel Dis."},{"issue":"10","key":"2025070707413689900_CIT0017","doi-asserted-by":"publisher","first-page":"1580-1588","DOI":"10.1016\/j.cgh.2017.03.031","article-title":"Improved long-term outcomes of patients with inflammatory bowel disease receiving proactive compared with reactive monitoring of serum concentrations of infliximab","volume":"15","author":"Papamichael","year":"2017","journal-title":"Clin. Gastroenterol. Hepatol."},{"issue":"12","key":"2025070707413689900_CIT0018","doi-asserted-by":"publisher","first-page":"1362-1374","DOI":"10.1111\/apt.17313","article-title":"Meta-analysis: The efficacy of therapeutic drug monitoring of anti-tnf-therapy in inflammatory bowel disease","volume":"57","author":"Sethi","year":"2023","journal-title":"Alim. Pharmacol. Ther."},{"issue":"5","key":"2025070707413689900_CIT0019","doi-asserted-by":"publisher","first-page":"1343","DOI":"10.1053\/j.gastro.2018.01.004","article-title":"Increasing infliximab dose based on symptoms, biomarkers, and serum drug concentrations does not increase clinical, endoscopic, and corticosteroid-free remission in patients with active luminal Crohn\u2019s disease","volume":"154","author":"D\u2019Haens","year":"2018","journal-title":"Gastroenterology."},{"issue":"7","key":"2025070707413689900_CIT0020","doi-asserted-by":"publisher","first-page":"1320","DOI":"10.1053\/j.gastro.2015.02.031","article-title":"Trough concentrations of infliximab guide dosing for patients with inflammatory bowel disease","volume":"148","author":"Vande Casteele","year":"2015","journal-title":"Gastroenterology."},{"issue":"4","key":"2025070707413689900_CIT0021","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1053\/j.gastro.2019.06.003","article-title":"Proactive monitoring of adalimumab trough concentration associated with increased clinical remission in children with Crohn\u2019s disease compared with reactive monitoring","volume":"157","author":"Assa","year":"2019","journal-title":"Gastroenterology."},{"issue":"1","key":"2025070707413689900_CIT0022","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1093\/ecco-jcc\/jjad121","article-title":"Durability of the first biologic in patients with Crohn\u2019s disease: a nationwide study from the epi-IIRN","volume":"18","author":"Atia","year":"2024","journal-title":"J Crohns Colitis."},{"issue":"3","key":"2025070707413689900_CIT0023","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1093\/ibd\/izae067","article-title":"Durability of the first biologic in children and adults with ulcerative colitis: a nationwide study from the epi-IIRN","volume":"31","author":"Atia","year":"2024","journal-title":"Inflamm Bowel Dis."},{"issue":"15","key":"2025070707413689900_CIT0024","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."},{"issue":"6","key":"2025070707413689900_CIT0025","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1016\/S2468-1253(24)00044-X","article-title":"Mechanisms and management of loss of response to anti-tnf therapy for patients with Crohn\u2019s disease: 3-year data from the prospective, multicentre pants cohort study","volume":"9","author":"Chanchlani","year":"2024","journal-title":"Lancet Gastroenterol. Hepatol."},{"issue":"6","key":"2025070707413689900_CIT0026","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1111\/imj.14150","article-title":"Immunomodulator use does not prevent first loss of response to anti-tumour necrosis factor alpha therapy in inflammatory bowel disease: long-term outcomes in a real-world cohort","volume":"49","author":"Varma","year":"2019","journal-title":"Intern Med J."},{"issue":"7","key":"2025070707413689900_CIT0027","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1016\/j.cgh.2015.02.017","article-title":"Effectiveness and safety of immunomodulators with anti-tnf therapy in Crohn\u2019s disease","volume":"13","author":"Osterman","year":"2025","journal-title":"Clin. Gastroenterol. Hepatol."},{"issue":"7","key":"2025070707413689900_CIT0028","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1093\/ecco-jcc\/jjz018","article-title":"Proactive therapeutic drug monitoring of adalimumab is associated with better long-term outcomes compared with standard of care in patients with inflammatory bowel disease","volume":"13","author":"Papamichael","year":"2019","journal-title":"J Crohns Colitis."},{"issue":"11","key":"2025070707413689900_CIT0029","doi-asserted-by":"publisher","first-page":"1996-2003","DOI":"10.1097\/MIB.0000000000000156","article-title":"Proactive therapeutic concentration monitoring of infliximab may improve outcomes for patients with inflammatory bowel disease: results from a pilot observational study","volume":"20","author":"Vaughn","year":"2014","journal-title":"Inflamm Bowel Dis."},{"issue":"3","key":"2025070707413689900_CIT0030","doi-asserted-by":"publisher","first-page":"otaa050","DOI":"10.1093\/crocol\/otaa050","article-title":"Proactive drug monitoring is associated with higher persistence to infliximab and adalimumab treatment and lower healthcare utilization compared with reactive and clinical monitoring","volume":"2","author":"Syed","year":"2020","journal-title":"Crohn\u2019s Colitis 360"},{"issue":"2","key":"2025070707413689900_CIT0031","doi-asserted-by":"publisher","first-page":"275-282","DOI":"10.1093\/ibd\/izaa073","article-title":"A systematic review on cost-effectiveness analyses of therapeutic drug monitoring for patients with inflammatory bowel disease: from immunosuppressive to anti-tnf therapy","volume":"27","author":"Yao","year":"2021","journal-title":"Inflamm Bowel Dis."},{"issue":"11","key":"2025070707413689900_CIT0032","doi-asserted-by":"publisher","first-page":"3069","DOI":"10.3390\/jcm13113069","article-title":"Benefits of biosimilars in the management of patients with inflammatory bowel disease: an international survey","volume":"13","author":"D\u2019Amico","year":"2024","journal-title":"J. Clin. Med."},{"issue":"1","key":"2025070707413689900_CIT0033","doi-asserted-by":"publisher","first-page":"103-111","DOI":"10.1093\/ibd\/izz113","article-title":"Proactive vs reactive therapeutic drug monitoring of infliximab in Crohn\u2019s disease: a cost-effectiveness analysis in a simulated cohort","volume":"26","author":"Negoescu","year":"2020","journal-title":"Inflamm Bowel Dis."},{"issue":"9","key":"2025070707413689900_CIT0034","doi-asserted-by":"publisher","first-page":"2074","DOI":"10.1016\/j.cgh.2021.11.030","article-title":"Steroid-free deep remission at one year does not prevent Crohn\u2019s disease progression: long-term data from the tailorix trial","volume":"20","author":"Laharie","year":"2022","journal-title":"Clin. Gastroenterol. Hepatol."}],"container-title":["Crohn's &amp; Colitis 360"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/crohnscolitis360\/advance-article-pdf\/doi\/10.1093\/crocol\/otaf028\/62903085\/otaf028.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/crohnscolitis360\/article-pdf\/7\/2\/otaf028\/62903085\/otaf028.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/crohnscolitis360\/article-pdf\/7\/2\/otaf028\/62903085\/otaf028.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T11:41:42Z","timestamp":1751888502000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/crohnscolitis360\/article\/doi\/10.1093\/crocol\/otaf028\/8109977"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4]]},"references-count":34,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,4,10]]}},"URL":"https:\/\/doi.org\/10.1093\/crocol\/otaf028","relation":{},"ISSN":["2631-827X"],"issn-type":[{"value":"2631-827X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,4]]},"published":{"date-parts":[[2025,4]]},"article-number":"otaf028"}}