{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T18:39:34Z","timestamp":1792089574831,"version":"4.4.0"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T00:00:00Z","timestamp":1702857600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Upadacitinib is a selective Janus kinase (JAK) inhibitor which is approved by the US Food and Drug Administration, the European Medicines Agency, as well as other agencies around the world for the treatment of several chronic inflammatory diseases, including rheumatic, dermatologic, and gastrointestinal diseases. Through inhibition of JAK, upadacitinib inhibits phosphorylation of downstream effector proteins, which consequently inhibits cytokine signaling for key pathways involved in inflammatory diseases. Upadacitinib more potently inhibits JAK1 than other JAK isoforms. The pharmacokinetics, pharmacodynamics, efficacy, and safety of upadacitinib were characterized in many clinical trials, which demonstrated the superiority of upadacitinib treatment over placebo or an active comparator in rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, non\u2010radiographic axial spondyloarthritis, atopic dermatitis, Crohn's disease, and ulcerative colitis. The safety profile of upadacitinib supported a favorable benefit\u2013risk profile across all the approved indications. In this article, we review the mechanism of action of upadacitinib and describe how the JAK\u2013STAT (Janus kinase\u2013signal transducers and activators of transcription) pathway is involved in the pathogenesis of several chronic and progressive immune\u2010mediated inflammatory diseases. In addition, this review also provides an overview of key clinical trials that were conducted as well as relevant data which supported the clinical development of upadacitinib and informed the recommended dose(s) in each of the approved indications.<\/jats:p>","DOI":"10.1111\/cts.13688","type":"journal-article","created":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T06:47:35Z","timestamp":1700549255000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":191,"title":["Upadacitinib: Mechanism of action, clinical, and translational science"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0959-2025","authenticated-orcid":false,"given":"Mohamed\u2010Eslam F.","family":"Mohamed","sequence":"first","affiliation":[{"name":"Clinical Pharmacology AbbVie  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4410-8131","authenticated-orcid":false,"given":"Sumit","family":"Bhatnagar","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology AbbVie  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9773-5670","authenticated-orcid":false,"given":"Julie M.","family":"Parmentier","sequence":"additional","affiliation":[{"name":"Precision Medicine AbbVie  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6709-1363","authenticated-orcid":false,"given":"Priscila","family":"Nakasato","sequence":"additional","affiliation":[{"name":"Medical Affairs AbbVie  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1883-2097","authenticated-orcid":false,"given":"Peter","family":"Wung","sequence":"additional","affiliation":[{"name":"Clinical Development AbbVie  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,18]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1068260"},{"key":"e_1_2_13_3_1","first-page":"3498","article-title":"JAK\/STAT pathway in pathology of rheumatoid arthritis (review)","volume":"20","author":"Ciobanu DA","year":"2020","journal-title":"Exp Ther Med"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-015-2961-7"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1615975"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40259-019-00333-w"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1995.tb07128.x"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s41927-018-0031-x"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.41032"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2022516"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2022-222608"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2212728"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)00581-5"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2021.3023"},{"key":"e_1_2_13_15_1","unstructured":"RINVOQ\u2122 (Upadacitinib) [US package insert]. North Chicago IL: AbbVie Inc. 2019."},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.2302\/kjm.2022-0015-IR"},{"key":"e_1_2_13_17_1","unstructured":"European Medicines Agency.Rinvoq (upadacitinib) assessment report. Procedure No. EMEA\/H\/C\/004760\/0000 (EMA\/608624\/2019 Corr. 1).2020."},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1513"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kead448"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-019-00855-0"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1375"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1414"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2008250"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2023.03.040"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.2340\/actadv.v103.5243"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjac157"},{"key":"e_1_2_13_27_1","first-page":"1398","article-title":"AB0421\u2009real\u2010world effectiveness of upadacitinib in patients with rheumatoid arthritis","volume":"82","author":"Diederik DC","year":"2023","journal-title":"Ann Rheum Dis"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1671"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-022-01191-6"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13146"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.15803"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2022-002735"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2109927"},{"key":"e_1_2_13_34_1","first-page":"1130","article-title":"Safety profile of upadacitinib in patients at risk of cardiovascular disease: integrated post hoc analysis of the SELECT phase III rheumatoid arthritis clinical programme","volume":"82","author":"Fleischmann R","year":"2023","journal-title":"Ann Rheum Dis"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.13688","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,24]],"date-time":"2024-01-24T13:42:58Z","timestamp":1706103778000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.13688"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,18]]},"references-count":33,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1111\/cts.13688"],"URL":"https:\/\/doi.org\/10.1111\/cts.13688","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,18]]},"assertion":[{"value":"2023-07-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13688"}}