ORIGINAL RESEARCH article
Front. Med.
Sec. Regulatory Science
Post-Marketing Surveillance of Upadacitinib: Multilevel Analysis of Venous Thromboembolism Reporting in Global Data and Rheumatoid Arthritis
Provisionally accepted
Renato Ferreira da Silva1*
Mariana Lobo1
Ana Rafaela Abreu1Juliana Pereira Macedo1Beatriz Mós1Carolina Ameijeiras Rodriguez1Inês Lourenço1Isabel Vieira1Jorge Junqueira Polónia1Luís Gouveia1Lurdes Silva1
Manuela Morato2Manuela Pinto3Mario Forrester1Marta Pereira4Nuno Miguel Rodrigues5Tayanny Biase1Inês Ribeiro1- 1Faculty of Medicine, University of Porto, Porto, Portugal
- 2Universidade do Porto Faculdade de Farmacia, Porto, Portugal
- 3Centro Hospitalar Universitario de Sao Joao, Porto, Portugal
- 4Centro Hospitalar Universitario de Santo Antonio, Porto, Portugal
- 5Unidade Local de Saude de Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal
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ABSTRACT Background: 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. Objective: To assess the post-marketing safety profile of upadacitinib in relation to VTE using global pharmacovigilance data. Methods: 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. Results: 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: –0.04). In 2023, disproportionality declined, particularly relative to other JAKi (ROR: 0.57; IC: –0.38). Conclusions: 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.
Keywords: Janus kinase inhibitors, Venous Thromboembolism, Pharmacovigilance, Drug-Related Side Effectsand Adverse Reactions, Arthritis, Rheumatoid, Adverse Drug Reaction Reporting Systems
Received: 11 Aug 2025; Accepted: 29 Oct 2025.
Copyright: © 2025 Ferreira da Silva, Lobo, Abreu, Macedo, Mós, Rodriguez, Lourenço, Vieira, Polónia, Gouveia, Silva, Morato, Pinto, Forrester, Pereira, Rodrigues, Biase and Ribeiro. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Renato Ferreira da Silva, renato.ivos@gmail.com
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