{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T04:09:39Z","timestamp":1791864579743,"version":"4.3.4"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T00:00:00Z","timestamp":1739232000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007834","name":"Natural Science Foundation of Ningbo Municipality","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007834","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Upadacitinib, a Janus kinase inhibitor, has been increasingly used over the past few years to treat moderate to severe ulcerative colitis and Crohn\u2019s disease in patients who are insufficiently responsive or intolerant to tumor necrosis factor (TNF) antibodies, demonstrating notable clinical efficacy. The long-term safety of upadacitinib in extensive populations remains unexplored. This study evaluates upadacitinib-related adverse events (AEs) utilizing data from the US Food and Drug Administration Adverse Event Reporting System (FAERS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We employed disproportionality analyses, including the proportional reporting ratio (PRR), reporting odds ratio (ROR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayesian geometric mean (EBGM) algorithms to identify signals of upadacitinib-associated AEs for treating inflammatory bowel disease (IBD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>From a total of 7,037,004 adverse event reports sourced from the FAERS database, 37,822 identified upadacitinib as the primary suspect drug in adverse drug events (ADEs), including 1,917 reports specifically related to the treatment of inflammatory bowel disease (IBD). The most commonly reported AEs were acne, product residue present, haematochezia, frequent bowel movements, flatulence, blood cholesterol increased, aligning with clinical trial outcomes. Notably, significant but unexpected AEs, such as rosacea, proctalgia, polyp, were also reported. Subgroup analysis indicated that the most prevalent AEs among the elderly included pulmonary embolism, cataract, and sepsis, whereas the 18\u201365 age group most frequently reported acne, abdominal pain, and nasopharyngitis. The median onset time for AEs related to upadacitinib was 41.00\u00a0days (interquartile range [IQR] 10\u2013141.5\u00a0days), with the majority occurring within 3\u00a0months of treatment initiation (n = 269, 66.09%), particularly in the first month (n = 171, 42.01%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings affirm clinical observations and reveal potential new AE signals for upadacitinib, underscoring the need for prospective clinical studies to verify these results and clarify their clinical relevance. This study contributes valuable evidence for ongoing safety evaluations of upadacitinib.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1436183","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T10:36:07Z","timestamp":1739270167000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Disproportionality analysis of upadacitinib-related adverse events in inflammatory bowel disease using the FDA adverse event reporting system"],"prefix":"10.3389","volume":"16","author":[{"given":"Shiyi","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xudong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongmei","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihong","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changbo","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3245","DOI":"10.1093\/rheumatology\/kead211","article-title":"Venous and arterial thromboembolic risk of Janus kinase inhibitors: a systematic review with meta-analysis","volume":"62","author":"Campanaro","year":"2023","journal-title":"Rheumatol. Oxf."},{"key":"B2","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1007\/s40744-023-00624-3","article-title":"Impact of upadacitinib on laboratory parameters and related adverse events in patients with RA: integrated data up to 6.5 years","volume":"11","author":"Charles-Schoeman","year":"2024","journal-title":"Rheumatol. Ther."},{"key":"B3","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1007\/bf03256733","article-title":"Comparison of sensitivity and timing of early signal detection of four frequently used signal detection methods","volume":"22","author":"Chen","year":"2012","journal-title":"Pharm. Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"2113","DOI":"10.1016\/S0140-6736(22)00581-5","article-title":"Upadacitinib as induction and maintenance therapy for moderately to severely active ulcerative colitis: results from three phase 3, multicentre, double-blind, randomised trials","volume":"399","author":"Danese","year":"2022","journal-title":"Lancet"},{"key":"B5","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1016\/S0140-6736(22)01212-0","article-title":"Upadacitinib for the treatment of active non-radiographic axial spondyloarthritis (SELECT-AXIS 2): a randomised, double-blind, placebo-controlled, phase 3 trial","volume":"400","author":"Deodhar","year":"2022","journal-title":"Lancet"},{"key":"B6","doi-asserted-by":"publisher","first-page":"2513","DOI":"10.1016\/S0140-6736(18)31116-4","article-title":"Safety and efficacy of upadacitinib in patients with active rheumatoid arthritis refractory to biologic disease-modifying anti-rheumatic drugs (SELECT-BEYOND): a double-blind, randomised controlled phase 3 trial","volume":"391","author":"Genovese","year":"2018","journal-title":"Lancet"},{"key":"B7","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1159\/000527422","article-title":"New and emerging treatments for inflammatory bowel disease","volume":"104","author":"Higashiyama","year":"2023","journal-title":"Digestion"},{"key":"B8","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/s41575-020-00360-x","article-title":"The four epidemiological stages in the global evolution of inflammatory bowel disease","volume":"18","author":"Kaplan","year":"2021","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"12445","DOI":"10.3390\/ijms232012445","article-title":"Etiology of IBD-is it still a mystery?","volume":"23","author":"Kofla-Dlubacz","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1966","DOI":"10.1056\/NEJMoa2212728","article-title":"Upadacitinib induction and maintenance therapy for Crohn's disease","volume":"388","author":"Loftus","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"912","DOI":"10.1002\/acr2.11479","article-title":"Cardiovascular and venous thromboembolic risk with janus kinase inhibitors in immune-mediated inflammatory diseases: a systematic review and meta-analysis of randomized trials","volume":"4","author":"Maqsood","year":"2022","journal-title":"ACR Open Rheumatol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1136\/annrheumdis-2020-218870","article-title":"Upadacitinib for psoriatic arthritis refractory to biologics: SELECT-PsA 2","volume":"80","author":"Mease","year":"2021","journal-title":"Ann. Rheum. Dis."},{"key":"B13","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1016\/j.jaad.2022.06.012","article-title":"Characterization of acne associated with upadacitinib treatment in patients with moderate-to-severe atopic dermatitis: a post hoc integrated analysis of 3 phase 3 randomized, double-blind, placebo-controlled trials","volume":"87","author":"Mendes-Bastos","year":"2022","journal-title":"J. Am. Acad. Dermatol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"34","DOI":"10.3390\/jcm13010034","article-title":"Reproductive safety issues of novel small molecules for the treatment of inflammatory bowel disease: a systematic review","volume":"13","author":"Monfared","year":"2023","journal-title":"J. Clin. Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"bbab347","DOI":"10.1093\/bib\/bbab347","article-title":"Detection algorithms and attentive points of safety signal using spontaneous reporting systems as a clinical data source","volume":"22","author":"Noguchi","year":"2021","journal-title":"Brief. Bioinform"},{"key":"B16","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1007\/s40265-023-01840-5","article-title":"Safety of janus kinase inhibitors in inflammatory bowel diseases","volume":"83","author":"Nunez","year":"2023","journal-title":"Drugs"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1270","DOI":"10.1016\/j.dld.2024.03.010","article-title":"Preventing and managing cardiovascular events in patients with inflammatory bowel diseases treated with small-molecule drugs, an international Delphi consensus","volume":"56","author":"Olivera","year":"2024","journal-title":"Dig. Liver Dis."},{"key":"B18","doi-asserted-by":"publisher","first-page":"2040622319838443","DOI":"10.1177\/2040622319838443","article-title":"Infliximab in inflammatory bowel disease","volume":"10","author":"Papamichael","year":"2019","journal-title":"Ther. Adv. Chronic Dis."},{"key":"B19","doi-asserted-by":"publisher","first-page":"2169","DOI":"10.1016\/S0140-6736(21)00589-4","article-title":"Safety and efficacy of upadacitinib in combination with topical corticosteroids in adolescents and adults with moderate-to-severe atopic dermatitis (AD Up): results from a randomised, double-blind, placebo-controlled, phase 3 trial","volume":"397","author":"Reich","year":"2021","journal-title":"Lancet"},{"key":"B20","article-title":"RINVOQ\u00ae(upadacitinib)","year":"2021","journal-title":"A extended-release tablets U. S. Prescr. Inf."},{"key":"B21","doi-asserted-by":"publisher","first-page":"796","DOI":"10.7150\/ijms.6048","article-title":"Data mining of the public version of the FDA adverse event reporting system","volume":"10","author":"Sakaeda","year":"2013","journal-title":"Int. J. Med. Sci."},{"key":"B22","doi-asserted-by":"publisher","first-page":"2123","DOI":"10.1053\/j.gastro.2020.01.047","article-title":"Efficacy and safety of upadacitinib in a randomized trial of patients with Crohn's disease","volume":"158","author":"Sandborn","year":"2020","journal-title":"Gastroenterology"},{"key":"B23","doi-asserted-by":"publisher","first-page":"113","DOI":"10.25122\/jml-2018-0075","article-title":"A review of the diagnosis, prevention, and treatment methods of inflammatory bowel disease","volume":"12","author":"Seyedian","year":"2019","journal-title":"J. Med. Life"},{"key":"B24","doi-asserted-by":"publisher","first-page":"i1621","DOI":"10.1093\/ecco-jcc\/jjad212.1009","article-title":"P879 comparative efficacy of biologics and small molecule therapies for the induction and maintenance of endoscopic and histological remission in ulcerative colitis: a systematic review and network meta-analysis","volume":"18","author":"Shehab","year":"2024","journal-title":"J. Crohn's Colitis"},{"key":"B25","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1016\/S2468-1253(22)00358-2","article-title":"Management of inflammatory bowel diseases in older adults","volume":"8","author":"Singh","year":"2023","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1016\/j.dld.2022.12.024","article-title":"Management of inflammatory bowel disease in the elderly: a review","volume":"55","author":"Sousa","year":"2023","journal-title":"Dig. Liver Dis."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/ecco-jcc\/jjac115","article-title":"European Crohn's and colitis guidelines on sexuality, Fertility, pregnancy, and lactation","volume":"17","author":"Torres","year":"2023","journal-title":"J. Crohns Colitis"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1570","DOI":"10.1053\/j.gastro.2020.12.031","article-title":"STRIDE-II: an update on the selecting therapeutic targets in inflammatory bowel disease (STRIDE) initiative of the international organization for the study of IBD (IOIBD): determining therapeutic goals for treat-to-target strategies in IBD","volume":"160","author":"Turner","year":"2021","journal-title":"Gastroenterology"},{"key":"B29","doi-asserted-by":"publisher","first-page":"2108","DOI":"10.1016\/S0140-6736(19)32534-6","article-title":"Efficacy and safety of upadacitinib in patients with active ankylosing spondylitis (SELECT-AXIS 1): a multicentre, randomised, double-blind, placebo-controlled, phase 2\/3 trial","volume":"394","author":"van der Heijde","year":"2019","journal-title":"Lancet"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1189389","DOI":"10.3389\/fphar.2023.1189389","article-title":"Risk of venous thromboembolism with janus kinase inhibitors in inflammatory immune diseases: a systematic review and meta-analysis","volume":"14","author":"Zhang","year":"2023","journal-title":"Front. Pharmacol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1338902","DOI":"10.3389\/fphar.2024.1338902","article-title":"Adverse drug events associated with linezolid administration: a real-world pharmacovigilance study from 2004 to 2023 using the FAERS database","volume":"15","author":"Zou","year":"2024","journal-title":"Front. Pharmacol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1436183\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T10:36:12Z","timestamp":1739270172000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1436183\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,11]]},"references-count":31,"alternative-id":["10.3389\/fphar.2025.1436183"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2025.1436183","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,11]]},"article-number":"1436183"}}