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). Conclusion 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.
Mós et al. (Mon,) studied this question.
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