Cardiovascular and Thromboembolic Risk With Upadacitinib in Spondyloarthritis and Inflammatory Bowel Disease: A Meta-Analysis of Randomized Controlled Trials

Immune-mediated inflammatory diseases (IMIDs), including axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), Crohn’s disease (CD), and ulcerative colitis (UC), share overlapping inflammatory pathways and frequently coexist, supporting the relevance of evaluating treatment safety across these conditions. Upadacitinib, a selective Janus kinase 1 inhibitor, is approved for multiple IMIDs; however, concerns regarding major adverse cardiovascular events (MACE) and venous thromboembolism (VTE) have emerged based on class-related safety signals. We conducted systematic review and meta-analysis of randomized controlled trials to assess the risk of MACE and VTE associated with upadacitinib compared with placebo or active comparators in patients with spondyloarthritis (SpA) and inflammatory bowel disease (IBD). A systematic search of PubMed, Embase, Cochrane Library, and ClinicalTrials.gov identified eligible trials. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Eight RCTs comprising 4,433 patients were included, of whom 2,868 received upadacitinib. Across studies, MACE and VTE events were rare in both treatment and control groups. Upadacitinib was not associated with an increased risk of MACE (RR 0.35; 95% CI 0.05–2.19; p = 0.259) or VTE (RR 0.31; 95% CI 0.04–2.55; p = 0.279) in patients with SpA and IBD, with no observed heterogeneity (I ² = 0%). However, the low number of events resulted in wide confidence intervals and limited precision, precluding definitive conclusions regarding cardiovascular and thromboembolic safety. Larger randomized controlled trials and long-term real-world studies are needed to further evaluate these outcomes.