{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T20:49:10Z","timestamp":1783111750868,"version":"3.54.6"},"reference-count":22,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: There is limited data regarding the association of anti-drug antibody (ADA) levels with the efficacy of anti-tumor necrosis factor (anti-TNF) therapy in patients with inflammatory bowel disease (IBD). We aimed to investigate the association between antibody to adalimumab (ATA) and antibody to infliximab (ATI) levels and treatment failure in IBD. Methods: This single-center, retrospective cohort study included consecutive IBD patients with ADA evaluated with a drug-tolerant assay between September 2012 and February 2023. A time-to-event analysis was performed for treatment failure, defined as the need for drug discontinuation due to primary non-response, loss of response, a serious adverse event, or an IBD-related surgery. Patients were followed from first positive ADA until treatment failure or the end of the follow-up (May 2024). Results: The study population consisted of 134 patients with IBD [n = 58 (43%) on adalimumab; n = 86, (64%) with Crohn\u2019s disease]. Multiple COX regression analysis identified higher ADA levels to be associated with treatment failure (HR: 1.034, 95%CI: 1.024\u20131.045, p &lt; 0.001). A ROC analysis identified an ATA and ATI level threshold of 5.2 U\/mL (AUC: 0.705; 95%CI: 0.569\u20130.841; p = 0.003; sensitivity: 64%; specificity: 82%) and 8.8 U\/mL (AUC: 0.809; 95%CI: 0.713\u20130.906; p &lt; 0.001; sensitivity: 69%; specificity: 93%), respectively, to distinguish patients with or without treatment failure. Conclusions: In this large retrospective cohort study, higher levels of ADA were associated with treatment failure to anti-TNF therapy in IBD. Moreover, we identified ATA and ATI level thresholds of 5.2 U\/mL and 8.8 U\/mL, respectively, to be associated with treatment failure.<\/jats:p>","DOI":"10.3390\/jcm15020547","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T11:45:33Z","timestamp":1767959133000},"page":"547","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Higher Anti-Drug Antibody Levels to Anti-Tumor Necrosis Factor Therapies Are Associated with Treatment Failure in Patients with Inflammatory Bowel Disease"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-2441-1160","authenticated-orcid":false,"given":"Alessandra","family":"Saraga","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Deyhim","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajay","family":"Gade","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8698-5992","authenticated-orcid":false,"given":"Grace","family":"Geeganage","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mostafa","family":"Soliman","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1774-9653","authenticated-orcid":false,"given":"Nathan David Vanshelboym","family":"Rothschild","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Zullow","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loren G.","family":"Rabinowitz","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie B.","family":"Grossberg","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam S.","family":"Cheifetz","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1497-0254","authenticated-orcid":false,"given":"Konstantinos","family":"Papamichael","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1002\/ueg2.12705","article-title":"Effectiveness and treatment persistence of vedolizumab compared to anti-tumour necrosis factor-\u03b1 in patients with Crohn\u2019s disease: A systematic literature review and meta-analysis","volume":"13","author":"Armuzzi","year":"2025","journal-title":"United Eur. 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