{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T17:33:59Z","timestamp":1770831239906,"version":"3.50.1"},"reference-count":27,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Future Leaders in IBD to A.R."},{"DOI":"10.13039\/100005565","name":"Janssen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005565","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["27862"],"award-info":[{"award-number":["27862"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Children\u2019s Intestinal and Liver Disease Foundation"},{"name":"Compute Ontario (computeontario.ca) and the Digital Research Alliance of Canada"},{"name":"Northbridge Financial Corporation Chair in Inflammatory Bowel Disease, a joint Hospital-University Chair between the University of Toronto, The Hospital for Sick Children, and the SickKids Foundation"},{"name":"Distinguished Clinical Chair in Pediatric Inflammatory Bowel Disease through the Faculty of Medicine, University of Ottawa"},{"name":"Northbridge Financial Corporation Chair in Inflammatory Bowel Disease, a joint Hospital-University Chair between the University of Toronto, The Hospital for Sick Children, and the SickKids Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>We aimed to build a serum proteomics-based model to predict primary nonresponse (PNR) to infliximab (IFX) in pediatric colonic inflammatory bowel disease, with early proactive therapeutic drug monitoring.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Children in the prospective Canadian Children IBD Network with ulcerative colitis (UC), inflammatory bowel disease unclassified (IBD-U), or colonic Crohn\u2019s disease (CD) with serum pre-IFX were eligible. We defined PNR as IFX cessation plus surgery\/drug switch within 6\u2009months. We compared clinical features between groups (Mann Whitney U, chi-square test). We measured serum proteins with Olink Inflammation\/Immune Response panels. We built a regularized regression (generalized linear model [GLM]) machine learning model and compared its performance with other models with 10-fold cross-validation repeated 10 times (receiver-operating characteristic\/precision-recall curves, predictive score separation). We ranked proteomic features by SHAP (SHapley Additive exPlanations) analysis. We hypothesized that treatment-na\u00efve serum would be more informative than treatment-exposed serum.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We included 96 patients: 71 UC\/IBD-U (23 nonresponders), 42 treatment-na\u00efve (12 nonresponders); and 25 CD, 19 treatment-na\u00efve. Pre\u2013third and pre\u2013fourth dose serum infliximab levels were similar and robust (&amp;gt;10\u2009\u00b5g\/mL) in primary nonresponders and responders. Predictive performance was superior for diagnostic, treatment-na\u00efve samples; the GLM showed good ability to separate primary nonresponders and responders. The GLM model on treatment-na\u00efve serum (area under the curve \u223c0.75) had better specificity to predict responders and included 21 proteins, with CSF1 and ITM2A top ranked. UC\/IBD-U responders more often were steroid refractory and received infliximab as first maintenance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>A serum proteomics linear model on treatment-na\u00efve serum best predicted PNR. Findings require external validation but suggest that the diagnostic\/pretreatment window may be key to understanding biology central to effective drug sequencing.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ibd\/izaf329","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T12:54:48Z","timestamp":1766062488000},"source":"Crossref","is-referenced-by-count":0,"title":["Primary infliximab failure in pediatric colonic inflammatory bowel disease: Development of a proteomics predictive model using a prospective Canadian cohort"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9538-3005","authenticated-orcid":false,"given":"Amanda","family":"Ricciuto","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Toronto , Toronto, Ontario,","place":["Canada"]},{"name":"Institute of Health Policy Management and Evaluation, University of Toronto , Toronto, Ontario,","place":["Canada"]},{"name":"Child Health Evaluative Sciences, SickKids Research Institute , Toronto, Ontario,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrei L","family":"Turinsky","sequence":"additional","affiliation":[{"name":"Centre for Computational Medicine, The Hospital for Sick Children , Toronto, ON,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8623-4665","authenticated-orcid":false,"given":"Anne M","family":"Griffiths","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Toronto , Toronto, Ontario,","place":["Canada"]},{"name":"Division of Gastroenterology, Hepatology and Nutrition, IBD Centre, The Hospital for Sick Children , Toronto, Ontario,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David R","family":"Mack","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital of Eastern Ontario, University of Ottawa , Ottawa, Ontario,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3458-4142","authenticated-orcid":false,"given":"Eytan","family":"Wine","sequence":"additional","affiliation":[{"name":"Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, University of Alberta , Edmonton, Alberta,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric I","family":"Benchimol","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Toronto , Toronto, Ontario,","place":["Canada"]},{"name":"Institute of Health Policy Management and Evaluation, University of Toronto , Toronto, Ontario,","place":["Canada"]},{"name":"Child Health Evaluative Sciences, SickKids Research Institute , Toronto, Ontario,","place":["Canada"]},{"name":"Division of Gastroenterology, Hepatology and Nutrition, IBD Centre, The Hospital for Sick Children , Toronto, Ontario,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6417-7583","authenticated-orcid":false,"given":"Wael","family":"El-Matary","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital Research Institute of Manitoba, Department of Pediatrics, University of Manitoba , Winnipeg, Manitoba,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hien Q","family":"Huynh","sequence":"additional","affiliation":[{"name":"Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, University of Alberta , Edmonton, Alberta,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas","family":"Carman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Toronto , Toronto, Ontario,","place":["Canada"]},{"name":"Division of Gastroenterology, Hepatology and Nutrition, IBD Centre, The Hospital for Sick Children , Toronto, Ontario,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer C","family":"deBruyn","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Alberta Children\u2019s Hospital, University of Calgary , Calgary, Alberta,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony R","family":"Otley","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Dalhousie University , Halifax, Nova Scotia,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter C","family":"Church","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Toronto , Toronto, Ontario,","place":["Canada"]},{"name":"Division of Gastroenterology, Hepatology and Nutrition, IBD Centre, The Hospital for Sick Children , Toronto, Ontario,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7269-8557","authenticated-orcid":false,"given":"Kevan","family":"Jacobson","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, BC Children\u2019s Hospital , Vancouver, British Columbia,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Low","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition, IBD Centre, The Hospital for Sick Children , Toronto, Ontario,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma","family":"Broer","sequence":"additional","affiliation":[{"name":"School of Medicine, University College Dublin , Dublin,","place":["Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sally","family":"Lawrence","sequence":"additional","affiliation":[{"name":"Division of 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