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These challenges demand treatment strategies that address both intestinal inflammation and the broader developmental needs of children.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Data sources<\/jats:title>\n                    <jats:p>This review summarizes current advances in small-molecule therapies for pIBD based on published clinical trials, real-world studies, and mechanistic investigations retrieved from PubMed and clinical trial registries. Special emphasis is placed on Janus kinase (JAK) inhibitors and sphingosine-1-phosphate (S1P) modulators, which represent the main translational research focus in pediatric IBD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>JAK inhibitors such as tofacitinib and upadacitinib have demonstrated promising efficacy in pediatric patients with refractory disease, although their use remains off-label worldwide. Long-term safety concerns persist, including infection risk, developmental effects, and potential risks of malignancy or major adverse cardiovascular events. S1P modulators such as ozanimod are under clinical evaluation in children, but robust long-term data are still lacking. Emerging technologies such as single-cell and spatial profiling have begun to reveal age-dependent remodeling of gut immune architecture, emphasizing the importance of developmentally informed therapeutic approaches.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Small-molecule therapies offer a promising and mechanistically precise direction for the management of pIBD. Future progress will depend on age-specific clinical trials, physiologically based pharmacokinetic modeling, and biomarker discovery through integrated multiomics. Collaborative multicenter research is essential to optimize the safety and efficacy of these agents in children.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1007\/s12519-025-01001-6","type":"journal-article","created":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T11:04:12Z","timestamp":1765019052000},"page":"212-224","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Small-molecule therapies for pediatric inflammatory bowel disease: toward precision medicine"],"prefix":"10.1007","volume":"22","author":[{"given":"Ying","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling-Fen","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0566-5859","authenticated-orcid":false,"given":"Xu","family":"Teng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,12,6]]},"reference":[{"key":"1001_CR1","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1038\/s41586-020-2025-2","volume":"578","author":"DB Graham","year":"2020","unstructured":"Graham DB, Xavier RJ. 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