{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T20:11:19Z","timestamp":1792440679259,"version":"4.5.0"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T00:00:00Z","timestamp":1692230400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    <jats:bold>Objective:<\/jats:bold>\n                    To mine the adverse drug event (ADE) signals of upadacitinib based on the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database to provide a reference for the safe clinical use of the drug.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    The ADE data for upadacitinib from Q1 2004 to Q1 2023 in the FAERS database were retrieved, and data mining was performed using the reporting odds ratio and proportional reporting ratio.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    A total of 21,213 ADE reports for the primary suspect drug upadacitinib were obtained, involving 444 ADEs. Patients aged \u226560\u00a0years (21.48%) and female (70.11%) patients were at a higher risk of ADEs with upadacitinib. After data cleaning, 182 ADE signals from 19 system organ classes (SOCs) were obtained. Six of these SOCs that occurred more frequently and were not mentioned in the drug labeling information included renal and urinary system (1.09%), reproductive and breast diseases (1.14%), ear and labyrinth disorders (0.57%), psychiatric disease (0.57%), blood and lymphatic system disorders (0.57%), and endocrine disorders (0.57%). The top ten most frequent ADE signals reported for upadacitinib were mainly related to: infections and infestations (7), investigations (2), and skin and subcutaneous tissue disorders (1). The top 10 ADEs in signal intensity ranking were lip neoplasm, ureteral neoplasm, eczema herpeticum, vulvar dysplasia, mediastinum neoplasm, eosinopenia, herpes zoster cutaneous disseminated, eye ulcer, acne cystic, and\n                    <jats:italic>Moraxella<\/jats:italic>\n                    infection. The top 10 high-frequency events leading to serious adverse events were urinary tract infection (2.74%), herpes zoster (1.63%), diverticulitis (1.19%), bronchitis (0.68%), nasopharyngitis (0.68%), localised infection (0.66%), nephrolithiasis (0.66%), pulmonary thrombosis (0.66%), blood cholesterol increased (0.55%), and\n                    <jats:italic>Pneumocystis jirovecii<\/jats:italic>\n                    pneumonia (0.53%).\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    Clinicians should be vigilant to upadacitinib-induced events in systems not covered in the drug labeling information and to new and highly signaled ADEs to ensure the safe and effective use of upadacitinib.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2023.1200254","type":"journal-article","created":{"date-parts":[[2023,8,18]],"date-time":"2023-08-18T01:23:01Z","timestamp":1692321781000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":26,"title":["A real-world pharmacovigilance analysis of FDA adverse event reporting system database for upadacitinib"],"prefix":"10.3389","volume":"14","author":[{"given":"Yan","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meihao","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,8,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1007\/s40265-017-0701-9","article-title":"JAK-STAT signaling as a target for inflammatory and autoimmune diseases: current and future prospects","volume":"77","author":"Banerjee","year":"2017","journal-title":"J. Drugs"},{"key":"B2","doi-asserted-by":"publisher","first-page":"4421","DOI":"10.1111\/bcp.14868","article-title":"Pharmacovigilance-based drug repurposing: the search for inverse signals via OpenVigil identifies putative drugs against viral respiratory infections","volume":"87","author":"Bohm","year":"2021","journal-title":"Br. J. Clin. Pharmacol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"e0157753","DOI":"10.1371\/journal.pone.0157753","article-title":"OpenVigil FDA - inspection of U.S. American adverse drug events pharmacovigilance data and novel clinical applications","volume":"11","author":"Bohm","year":"2016","journal-title":"PLoS One"},{"key":"B4","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1093\/rheumatology\/key339","article-title":"Clinical significance of Janus Kinase inhibitor selectivity","volume":"58","author":"Choy","year":"2019","journal-title":"Rheumatol. Oxf."},{"key":"B5","doi-asserted-by":"publisher","first-page":"5023","DOI":"10.1021\/jm401490p","article-title":"Discovery and development of Janus kinase (JAK) inhibitors for inflammatory diseases","volume":"57","author":"Clark","year":"2014","journal-title":"J. Med. Chem."},{"key":"B6","doi-asserted-by":"publisher","first-page":"ii24","DOI":"10.1093\/rheumatology\/keaa895","article-title":"The safety of JAK-1 inhibitors","volume":"60","author":"Clarke","year":"2021","journal-title":"Rheumatol. Oxf."},{"key":"B7","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1136\/annrheumdis-2020-218510","article-title":"Safety profile of upadacitinib in rheumatoid arthritis: integrated analysis from the SELECT phase III clinical programme","volume":"80","author":"Cohen","year":"2021","journal-title":"Ann. Rheum. Dis."},{"key":"B8","doi-asserted-by":"publisher","first-page":"4180","DOI":"10.1111\/bcp.15361","article-title":"Thromboembolic events in janus kinase inhibitors: A pharmacovigilance study from 2012 to 2021 based on the Food and drug administration's adverse event reporting system","volume":"88","author":"Dong","year":"2022","journal-title":"Br. J. Clin. Pharmacol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"e002012","DOI":"10.1136\/rmdopen-2021-002012","article-title":"Long-term safety and efficacy of upadacitinib or adalimumab in patients with rheumatoid arthritis: results through 3 years from the SELECT-COMPARE study","volume":"8","author":"Fleischmann","year":"2022","journal-title":"RMD Open"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1551","DOI":"10.1007\/s00296-017-3726-1","article-title":"Prevalence of rheumatoid arthritis in the United States adult population in healthcare claims databases, 2004-2014","volume":"37","author":"Hunter","year":"2017","journal-title":"Rheumatol. Int."},{"key":"B11","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1002\/pds.964","article-title":"Comparison of data mining methodologies using Japanese spontaneous reports","volume":"13","author":"Kubota","year":"2004","journal-title":"Pharmacoepidemiol Drug Saf."},{"key":"B12","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/S2468-1253(21)00377-0","article-title":"Efficacy and safety of biologics and small molecule drugs for patients with moderate-to-severe ulcerative colitis: A systematic review and network meta-analysis","volume":"7","author":"Lasa","year":"2022","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1186\/s12920-019-0502-y","article-title":"LncRNA-miRNA-mRNA expression variation profile in the urine of calcium oxalate stone patients","volume":"12","author":"Liang","year":"2019","journal-title":"BMC Med. Genomics"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1056\/NEJMoa2022516","article-title":"Trial of upadacitinib and adalimumab for psoriatic arthritis","volume":"384","author":"McInnes","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1038\/s41577-021-00603-1","article-title":"Immune-mediated inflammatory disease therapeutics: past, present and future","volume":"21","author":"McInnes","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/s41927-018-0031-x","article-title":"In vitro and in vivo characterization of the JAK1 selectivity of upadacitinib (ABT-494)","volume":"2","author":"Parmentier","year":"2018","journal-title":"BMC Rheumatol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1505","DOI":"10.1080\/14740338.2020.1799975","article-title":"A real-world disproportionality analysis of FDA Adverse Event Reporting System (FAERS) events for baricitinib","volume":"19","author":"Peng","year":"2020","journal-title":"Expert Opin. Drug Saf."},{"key":"B18","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":"B19","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":"B20","doi-asserted-by":"publisher","first-page":"2139","DOI":"10.1053\/j.gastro.2020.02.030","article-title":"Efficacy of upadacitinib in a randomized trial of patients with active ulcerative colitis","volume":"158","author":"Sandborn","year":"2020","journal-title":"Gastroenterology"},{"key":"B21","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1007\/s40264-021-01082-y","article-title":"Reporting of thromboembolic events with JAK inhibitors: analysis of the FAERS database 2010-2019","volume":"44","author":"Setyawan","year":"2021","journal-title":"Drug Saf."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.1007\/s40264-018-0706-7","article-title":"A critical evaluation of safety signal analysis using algorithmic standardised MedDRA queries","volume":"41","author":"Tieu","year":"2018","journal-title":"Drug Saf."},{"key":"B23","doi-asserted-by":"publisher","first-page":"106210","DOI":"10.1016\/j.intimp.2020.106210","article-title":"The role of JAK\/STAT signaling pathway and its inhibitors in diseases","volume":"80","author":"Xin","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1056\/NEJMoa2109927","article-title":"Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis","volume":"386","author":"Ytterberg","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"B25","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1186\/s40425-019-0754-2","article-title":"Endocrine toxicity of immune checkpoint inhibitors: A real-world study leveraging US Food and drug administration adverse events reporting system","volume":"7","author":"Zhai","year":"2019","journal-title":"J. Immunother. Cancer"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1200254\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,18]],"date-time":"2023-08-18T01:23:04Z","timestamp":1692321784000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1200254\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,17]]},"references-count":25,"alternative-id":["10.3389\/fphar.2023.1200254"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2023.1200254","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,17]]},"article-number":"1200254"}}