{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T16:42:13Z","timestamp":1772556133409,"version":"3.50.1"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"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. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Upadacitinib is an oral Janus kinase 1 (JAK1) selective inhibitor approved for the treatment of rheumatoid arthritis (RA) and other immune-mediated inflammatory diseases. Concerns have emerged regarding a potential increased risk of venous thromboembolism (VTE) with JAK inhibitors (JAKi), though real-world evidence remains limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To assess the post-marketing safety profile of upadacitinib in relation to VTE using global pharmacovigilance data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a disproportionality analysis using Individual Case Safety Reports (ICSRs) from VigiBase, accessed via VigiLyze, including all reports up to February 20, 2025. Upadacitinib was compared with: (i) all other medicines; (ii) other second-line advanced RA therapies (bDMARDs and tsDMARDs); and (iii) other JAKi (baricitinib, tofacitinib, filgotinib). Reporting Odds Ratios (ROR) and Information Components (IC), with 95% confidence intervals, were calculated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Descriptive analyses identified 678 VTE cases with upadacitinib, predominantly affecting women (68.1%), with a median age of 63 years. Most were classified as serious (91.2%), although fatal outcomes were less frequent than with comparators. In disproportionality analyses, upadacitinib showed a significant signal versus all medicines (ROR: 2.08; IC: 1.04) and versus other second-line therapies (ROR: 1.40; IC: 0.41), but not versus other JAKi (ROR: 0.98; IC: \u20130.04). In 2023, disproportionality declined, particularly relative to other JAKi (ROR: 0.57; IC: \u20130.38).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Upadacitinib-related VTE cases display distinct clinical characteristics. These findings support continued pharmacovigilance and the need for robust real-world studies to clarify absolute and comparative risks, inform regulation, and guide personalised therapeutic strategies in RA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2025.1683751","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T06:24:38Z","timestamp":1764570278000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Post-marketing surveillance of upadacitinib: multilevel analysis of venous thromboembolism reporting in global data and rheumatoid arthritis"],"prefix":"10.3389","volume":"12","author":[{"given":"Renato","family":"Ferreira-da-Silva","sequence":"first","affiliation":[]},{"given":"Mariana","family":"Lobo","sequence":"additional","affiliation":[]},{"given":"Ana Rafaela","family":"Abreu","sequence":"additional","affiliation":[]},{"given":"Juliana","family":"Pereira-Macedo","sequence":"additional","affiliation":[]},{"given":"Beatriz","family":"M\u00f3s","sequence":"additional","affiliation":[]},{"given":"Carolina Ameijeiras","family":"Rodriguez","sequence":"additional","affiliation":[]},{"given":"In\u00eas Mariana","family":"Louren\u00e7o","sequence":"additional","affiliation":[]},{"given":"Isabel","family":"Vieira","sequence":"additional","affiliation":[]},{"given":"Jorge Junqueira","family":"Pol\u00f3nia","sequence":"additional","affiliation":[]},{"given":"Lu\u00eds","family":"Gouveia","sequence":"additional","affiliation":[]},{"given":"Lurdes","family":"Silva","sequence":"additional","affiliation":[]},{"given":"Manuela","family":"Morato","sequence":"additional","affiliation":[]},{"given":"Manuela","family":"Pinto","sequence":"additional","affiliation":[]},{"given":"Mario","family":"Forrester","sequence":"additional","affiliation":[]},{"given":"Marta","family":"Pereira","sequence":"additional","affiliation":[]},{"given":"Nuno","family":"Rodrigues","sequence":"additional","affiliation":[]},{"given":"Tayanny","family":"Biase","sequence":"additional","affiliation":[]},{"given":"In\u00eas","family":"Ribeiro","sequence":"additional","affiliation":[]}],"member":"1965","published-online":{"date-parts":[[2025,12,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/nrrheum.2015.167","article-title":"Type I\/II cytokines, JAKs, and new strategies for treating autoimmune diseases.","volume":"12","author":"Schwartz","year":"2016","journal-title":"Nat Rev Rheumatol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1038\/s41584-021-00726-8","article-title":"Janus kinase-targeting therapies in rheumatology: a mechanisms-based approach.","volume":"18","author":"Tanaka","year":"2022","journal-title":"Nat Rev Rheumatol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2021-326390.","article-title":"Efficacy of biological therapies and small molecules in moderate to severe ulcerative colitis: systematic review and network meta-analysis.","author":"Burr","year":"2022","journal-title":"Gut."},{"key":"B4","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1136\/annrheumdis-2024-eular.1416","article-title":"POS0639 Benefit\u2013risk analysis of upadacitinib versus adalimumab in patients with rheumatoid arthritis and higher or lower risk of cardiovascular disease.","volume":"83","author":"Burmester","year":"2024","journal-title":"Ann Rheum Dis."},{"key":"B5","volume-title":"Drug Trials Snapshots: Rinvoq [Internet].","year":"2019"},{"key":"B6","volume-title":"Rinvoq: EPAR - 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