{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:49:32Z","timestamp":1792784972149,"version":"4.5.0"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T00:00:00Z","timestamp":1642982400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T00:00:00Z","timestamp":1642982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Wolfe Medical Research Chair in Pharmacogenomics"},{"name":"Ontario Research Fund-Research Excellence Grant"},{"DOI":"10.13039\/100008958","name":"Lawson Health Research Institute","doi-asserted-by":"publisher","award":["IRF-31-20"],"award-info":[{"award-number":["IRF-31-20"]}],"id":[{"id":"10.13039\/100008958","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The interleukin-6 family cytokine, oncostatin-M (OSM) has been associated with response to tumor necrosis factor-\u03b1 antagonists (anti-TNFs) in small cohorts of patients with inflammatory bowel disease (IBD). We aimed to evaluate the association between plasma OSM concentrations and response to anti-TNFs (infliximab and adalimumab) in both ulcerative colitis (UC) and Crohn\u2019s disease (CD). A retrospective cohort study was conducted in patients with IBD with a history of anti-TNF exposure. Blood samples, collected prior to anti-TNF exposure, were analyzed by enzyme-linked immunosorbent assay for the presence and quantity of OSM. Clinical remission was assessed at 1-year post anti-TNF exposure in addition to the occurrence of surgery, hospitalization, corticosteroid use, and adverse drug events. Lastly the threshold OSM plasma concentration associated with anti-TNF non-response was assessed by receiver operator characteristic (ROC) curve analysis.\n Patients with IBD (CD, n\u2009=\u200982; UC, n\u2009=\u200940) were assessed. In both UC and CD, mean pre-treatment OSM concentrations were significantly lower in those who achieved clinical remission at 1-year (p\u2009&lt;\u20090.0001). A threshold plasma OSM concentration of 168.7\u00a0pg\/ml and 233.6\u00a0pg\/ml respectively separated those who achieved clinical remission at 1-year on an anti-TNF from those who did not in CD and UC respectively (CD: area under the receiver operator characteristic curve, AUROC\u2009=\u20090.880, 95% CI 0.79\u20130.96; UC: AUROC\u2009=\u20090.938, 95% CI 0.87\u20131.00). High OSM concentrations were associated with anti-TNF discontinuation and use of rescue steroids in CD and UC. High pre-treatment OSM concentrations identify IBD patients at-risk of anti-TNF non-response at 1-year as well as other deleterious clinical outcomes.<\/jats:p>","DOI":"10.1038\/s41598-022-05208-9","type":"journal-article","created":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T06:03:57Z","timestamp":1643004237000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["High oncostatin M predicts lack of clinical remission for patients with inflammatory bowel disease on tumor necrosis factor \u03b1 antagonists"],"prefix":"10.1038","volume":"12","author":[{"given":"Angela","family":"Guo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron","family":"Ross","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilesh","family":"Chande","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"Gregor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry","family":"Ponich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reena","family":"Khanna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Sey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Beaton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard B.","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aze","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,24]]},"reference":[{"issue":"9","key":"5208_CR1","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1056\/NEJMoa030815","volume":"350","author":"BE Sands","year":"2004","unstructured":"Sands, B. E. et al. Infliximab maintenance therapy for fistulizing Crohn\u2019s disease. N. Engl. J. Med. 350(9), 876\u2013885 (2004).","journal-title":"N. Engl. J. Med."},{"issue":"suppl 1","key":"5208_CR2","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1159\/000502816","volume":"101","author":"P Juillerat","year":"2020","unstructured":"Juillerat, P., Manz, M., Sauter, B., Zeitz, J. & Vavricka, S. R. Therapies in inflammatory bowel disease patients with extraintestinal manifestations. Digestion 101(suppl 1), 83\u201397 (2020).","journal-title":"Digestion"},{"issue":"10","key":"5208_CR3","doi-asserted-by":"publisher","first-page":"1291","DOI":"10.1111\/apt.14030","volume":"45","author":"A Cholapranee","year":"2017","unstructured":"Cholapranee, A., Hazlewood, G. S., Kaplan, G. G., Peyrin-Biroulet, L. & Ananthakrishnan, A. N. Systematic review with meta-analysis: Comparative efficacy of biologics for induction and maintenance of mucosal healing in Crohn\u2019s disease and ulcerative colitis controlled trials. Aliment Pharmacol. Ther. 45(10), 1291\u20131302 (2017).","journal-title":"Aliment Pharmacol. Ther."},{"issue":"4","key":"5208_CR4","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1038\/ajg.2011.103","volume":"106","author":"H Yanai","year":"2011","unstructured":"Yanai, H. & Hanauer, S. B. Assessing response and loss of response to biological therapies in IBD. Am. J. Gastroenterol. 106(4), 685\u2013698 (2011).","journal-title":"Am. J. Gastroenterol."},{"issue":"1","key":"5208_CR5","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.autrev.2013.06.002","volume":"13","author":"S Ben-Horin","year":"2014","unstructured":"Ben-Horin, S., Kopylov, U. & Chowers, Y. Optimizing anti-TNF treatments in inflammatory bowel disease. Autoimmun. Rev. 13(1), 24\u201330 (2014).","journal-title":"Autoimmun. Rev."},{"issue":"7","key":"5208_CR6","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1111\/apt.14550","volume":"47","author":"A Barr\u00e9","year":"2018","unstructured":"Barr\u00e9, A., Colombel, J.-F. & Ungaro, R. Review article: predictors of response to vedolizumab and ustekinumab in inflammatory bowel disease. Aliment Pharmacol. Ther. 47(7), 896\u2013905 (2018).","journal-title":"Aliment Pharmacol. Ther."},{"issue":"10","key":"5208_CR7","doi-asserted-by":"publisher","first-page":"1143","DOI":"10.1111\/apt.12727","volume":"39","author":"DT Rubin","year":"2014","unstructured":"Rubin, D. T., Mody, R., Davis, K. L. & Wang, C. C. Real-world assessment of therapy changes, suboptimal treatment and associated costs in patients with ulcerative colitis or Crohn\u2019s disease. Aliment Pharmacol. Ther. 39(10), 1143\u20131155 (2014).","journal-title":"Aliment Pharmacol. Ther."},{"issue":"1","key":"5208_CR8","doi-asserted-by":"publisher","first-page":"e0227914","DOI":"10.1371\/journal.pone.0227914","volume":"15","author":"A Armuzzi","year":"2020","unstructured":"Armuzzi, A. DiBonaventura Md, Tarallo M, Lucas J, Bluff D, Hoskin B, Bargo D, Cappelleri JC, Quirk D, Salese L: Treatment patterns among patients with moderate-to-severe ulcerative colitis in the United States and Europe. PLoS ONE 15(1), e0227914 (2020).","journal-title":"PLoS ONE"},{"key":"5208_CR9","unstructured":"Information CIoH: Prescribed drug spending in Canada, 2013: A focus on public drug programs. In: Canadian Institute of Health Information. 2014."},{"issue":"5","key":"5208_CR10","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1053\/j.gastro.2015.03.001","volume":"148","author":"B Bressler","year":"2015","unstructured":"Bressler, B. et al. Clinical practice guidelines for the medical management of nonhospitalized ulcerative colitis: The Toronto consensus. Gastroenterology 148(5), 1035-1058.e1033 (2015).","journal-title":"Gastroenterology"},{"issue":"3","key":"5208_CR11","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1093\/jcag\/gwz019","volume":"2","author":"R Panaccione","year":"2019","unstructured":"Panaccione, R. et al. Canadian association of gastroenterology clinical practice guideline for the management of luminal Crohn\u2019s disease. J. Can. Assoc. Gastroenterol. 2(3), e1\u2013e34 (2019).","journal-title":"J. Can. Assoc. Gastroenterol."},{"issue":"6","key":"5208_CR12","doi-asserted-by":"publisher","first-page":"1268","DOI":"10.1016\/j.cgh.2019.10.035","volume":"18","author":"NH Nguyen","year":"2020","unstructured":"Nguyen, N. H., Singh, S. & Sandborn, W. J. Positioning therapies in the management of Crohn\u2019s disease. Clin. Gastroenterol. Hepatol. 18(6), 1268\u20131279 (2020).","journal-title":"Clin. Gastroenterol. Hepatol."},{"issue":"13","key":"5208_CR13","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1056\/NEJMoa1905725","volume":"381","author":"BE Sands","year":"2019","unstructured":"Sands, B. E. et al. Vedolizumab versus adalimumab for moderate-to-severe ulcerative colitis. N. Engl. J. Med. 381(13), 1215\u20131226 (2019).","journal-title":"N. Engl. J. Med."},{"issue":"5","key":"5208_CR14","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1038\/nrgastro.2016.208","volume":"14","author":"MF Neurath","year":"2017","unstructured":"Neurath, M. F. Current and emerging therapeutic targets for IBD. Nat. Rev. Gastroenterol. Hepatol. 14(5), 269\u2013278 (2017).","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"5208_CR15","doi-asserted-by":"publisher","first-page":"512103","DOI":"10.1155\/2013\/512103","volume":"2013","author":"CD Richards","year":"2013","unstructured":"Richards, C. D. The enigmatic cytokine oncostatin M and roles in disease. ISRN Inflamm. 2013, 512103 (2013).","journal-title":"ISRN Inflamm."},{"issue":"5","key":"5208_CR16","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1038\/nm.4307","volume":"23","author":"NR West","year":"2017","unstructured":"West, N. R. et al. Oncostatin M drives intestinal inflammation and predicts response to tumor necrosis factor-neutralizing therapy in patients with inflammatory bowel disease. Nat. Med. 23(5), 579\u2013589 (2017).","journal-title":"Nat. Med."},{"issue":"2","key":"5208_CR17","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1111\/apt.15870","volume":"52","author":"L Bertani","year":"2020","unstructured":"Bertani, L. et al. Serum oncostatin M at baseline predicts mucosal healing in Crohn\u2019s disease patients treated with infliximab. Aliment Pharmacol. Ther. 52(2), 284\u2013291 (2020).","journal-title":"Aliment Pharmacol. Ther."},{"issue":"3","key":"5208_CR18","doi-asserted-by":"publisher","first-page":"otz026","DOI":"10.1093\/crocol\/otz026","volume":"1","author":"P Minar","year":"2019","unstructured":"Minar, P. et al. Elevated pretreatment plasma oncostatin M is associated with poor biochemical response to infliximab. Crohn\u2019s Colitis 360 1(3), otz026 (2019).","journal-title":"Crohn's Colitis 360"},{"key":"5208_CR19","doi-asserted-by":"crossref","unstructured":"Verstockt S, Verstockt B, Machiels K, Vancamelbeke M, Ferrante M, Cleynen I, De Hertogh G, Vermeire S: Oncostatin M is a biomarker of diagnosis, worse disease prognosis, and therapeutic nonresponse in inflammatory bowel disease. Inflamm. Bowel Dis. 27(10):1564-1575 (2021).","DOI":"10.1093\/ibd\/izab032"},{"issue":"3","key":"5208_CR20","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1002\/bimj.200710415","volume":"50","author":"MD Ruopp","year":"2008","unstructured":"Ruopp, M. D., Perkins, N. J., Whitcomb, B. W. & Schisterman, E. F. Youden Index and optimal cut-point estimated from observations affected by a lower limit of detection. Biometr. J. Biometrische Zeitschrift 50(3), 419\u2013430 (2008).","journal-title":"Biometr. J. Biometrische Zeitschrift"},{"issue":"11","key":"5208_CR21","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1080\/14728222.2019.1677608","volume":"23","author":"S Verstockt","year":"2019","unstructured":"Verstockt, S., Verstockt, B. & Vermeire, S. Oncostatin M as a new diagnostic, prognostic and therapeutic target in inflammatory bowel disease (IBD). Expert Opin. Ther. Targets 23(11), 943\u2013954 (2019).","journal-title":"Expert Opin. Ther. Targets"},{"issue":"5","key":"5208_CR22","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/j.cytogfr.2015.07.006","volume":"26","author":"HM Hermanns","year":"2015","unstructured":"Hermanns, H. M. Oncostatin M and interleukin-31: Cytokines, receptors, signal transduction and physiology. Cytokine Growth Factor Rev. 26(5), 545\u2013558 (2015).","journal-title":"Cytokine Growth Factor Rev."},{"issue":"7","key":"5208_CR23","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1093\/ecco-jcc\/jjx003","volume":"11","author":"LCS De Vries","year":"2017","unstructured":"De Vries, L. C. S., Wildenberg, M. E., De Jonge, W. J. & D\u2019Haens, G. R. The future of Janus kinase inhibitors in inflammatory bowel disease. J. Crohn\u2019s Colitis 11(7), 885\u2013893 (2017).","journal-title":"J. Crohn's Colitis"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-05208-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-05208-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-05208-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T15:59:51Z","timestamp":1669305591000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-05208-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,24]]},"references-count":23,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["5208"],"URL":"https:\/\/doi.org\/10.1038\/s41598-022-05208-9","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,24]]},"assertion":[{"value":"2 September 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 January 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 January 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1185"}}