{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T04:57:19Z","timestamp":1768539439838,"version":"3.49.0"},"reference-count":40,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Vedolizumab and ustekinumab are increasingly used off-label in pediatric inflammatory bowel disease (IBD) unresponsive or refractory to anti\u2013TNF\u03b1 therapy. Despite their increasing use in clinical practice, evidence in the pediatric population remains limited, especially regarding therapeutic exposure thresholds and the clinical utility of therapeutic drug monitoring (TDM). Methods: We report a series of five pediatric cases with Crohn\u2019s disease or ulcerative colitis treated with ustekinumab or vedolizumab after anti-TNF\u03b1 failure. Trough drug concentrations, anti-drug antibodies (ADAs), clinical scores (PCDAI\/PUCAI), biomarkers (fecal calprotectin, C-reactive protein), and endoscopic findings were assessed longitudinally. Results: In all cases, we observed recurrent discordance between clinical indices (PCDAI\/PUCAI), biochemical markers, and endoscopic activity. Clinical improvement frequently correlated with trough concentrations above commonly cited adult-derived reference ranges (&gt;15 \u00b5g\/mL for vedolizumab; &gt;3 \u00b5g\/mL for ustekinumab), although this alignment was not uniform across patients. Notably, one patient developed high-titre ADAs with undetectable ustekinumab levels, yet remained clinically stable, suggesting substantial interindividual variability in pharmacokinetics, immunogenicity, and disease control. Conclusions: Ustekinumab and vedolizumab are promising off-label options for pediatric refractory IBD. In this case series, TDM contributed to the interpretation of pharmacokinetic variability and immunogenicity, offering contextual insights that may support dose adjustments and therapeutic decision-making. Integrating TDM with clinical, biochemical, and endoscopic monitoring may improve optimize individualized treatment in this complex and vulnerable patient group.<\/jats:p>","DOI":"10.3390\/ph19010154","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T11:13:21Z","timestamp":1768475601000},"page":"154","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Off-Label Ustekinumab and Vedolizumab in Pediatric Anti-TNF\u03b1 Refractory IBD: Therapeutic Drug Monitoring Insights from a Case Series"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2837-5248","authenticated-orcid":false,"given":"Stefania","family":"Cheli","sequence":"first","affiliation":[{"name":"ICPS, Pharmacovigilance & Clinical Research, Department of Biomedical and Clinical Sciences, University Hospital Luigi Sacco, ASST Fatebenefratelli Sacco, Universit\u00e0 degli Studi di Milano, 20157 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Mosini","sequence":"additional","affiliation":[{"name":"ICPS, Pharmacovigilance & Clinical Research, Department of Biomedical and Clinical Sciences, University Hospital Luigi Sacco, ASST Fatebenefratelli Sacco, Universit\u00e0 degli Studi di Milano, 20157 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3513-9593","authenticated-orcid":false,"given":"Vera","family":"Battini","sequence":"additional","affiliation":[{"name":"ICPS, Pharmacovigilance & Clinical Research, Department of Biomedical and Clinical Sciences, University Hospital Luigi Sacco, ASST Fatebenefratelli Sacco, Universit\u00e0 degli Studi di Milano, 20157 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla","family":"Carnovale","sequence":"additional","affiliation":[{"name":"ICPS, Pharmacovigilance & Clinical Research, Department of Biomedical and Clinical Sciences, University Hospital Luigi Sacco, ASST Fatebenefratelli Sacco, Universit\u00e0 degli Studi di Milano, 20157 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonia","family":"Radice","sequence":"additional","affiliation":[{"name":"ICPS, Pharmacovigilance & Clinical Research, Department of Biomedical and Clinical Sciences, University Hospital Luigi Sacco, ASST Fatebenefratelli Sacco, Universit\u00e0 degli Studi di Milano, 20157 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Lebiu","sequence":"additional","affiliation":[{"name":"Pediatric Department Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Cattoni","sequence":"additional","affiliation":[{"name":"Pediatric Department Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanna","family":"Zuin","sequence":"additional","affiliation":[{"name":"Pediatric Department Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emilio","family":"Clementi","sequence":"additional","affiliation":[{"name":"ICPS, Pharmacovigilance & Clinical Research, Department of Biomedical and Clinical Sciences, University Hospital Luigi Sacco, ASST Fatebenefratelli Sacco, Universit\u00e0 degli Studi di Milano, 20157 Milan, Italy"},{"name":"Scientific Institute, IRCCS E. Medea, 23842 Bosisio Parini, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1080\/00365521.2020.1722738","article-title":"Sustained clinical benefit, improved quality of life, and reduced intestinal surgery from maintenance infliximab treatment in inflammatory bowel disease","volume":"55","author":"Hossain","year":"2020","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"101","DOI":"10.2147\/CEG.S4512","article-title":"The impact of biologics on health-related quality of life in patients with inflammatory bowel disease","volume":"2","author":"Vogelaar","year":"2009","journal-title":"Clin. Exp. 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