Risk of Malignancies and Major Adverse Cardiovascular Events Related to JAK Inhibitors in Rheumatoid Arthritis: A Meta-Analysis.

This meta-analysis evaluated the risk of malignancies and major adverse cardiovascular events (MACE) associated with the use of JAK inhibitors in patients with RA through a comprehensive meta-analysis of available clinical trials. A systematic search was conducted in PubMed, EMBASE, and Web of Science from inception to February 7, 2025, to identify relevant clinical trials. Data on malignancies and MACE incidence were extracted, and pooled risk ratios (RR) were calculated using a random-effects model. A total of 18 studies (N = 111,260) met the inclusion criteria. JAK inhibitors were associated with a significantly increased risk of malignancies excluding NMSC (RR = 1.30, 95%CI: 1.05, 1.60; P = 0.016), NMSC (RR = 1.54, 95%CI: 1.23, 1.93; P < 0.01), overall malignancies (RR = 1.53, 95%CI: 1.18, 2.00; P = 0.002), lung cancer (RR = 1.52, 95%CI: 1.11, 2.08; P = 0.009), lymphoma (RR = 3.69, 95%CI: 1.19, 11.42; P = 0.024), non-small cell lung cancer (RR = 1.70, 95%CI: 1.01, 2.86; P = 0.047), cutaneous squamous cell carcinoma (RR = 2.30, 95%CI: 1.44, 3.65; P < 0.01), and thyroid cancer (RR = 7.51, 95%CI: 1.39, 40.74; P = 0.019). In contrast, JAK inhibitors did not significantly alter the risk of MACE (RR = 0.75, 95%CI: 0.38, 1.45; P = 0.390), venous thromboembolism (VTE) (RR = 1.52, 95%CI: 0.90, 2.56; P = 0.117), or deep vein thrombosis (DVT) (RR = 1.77, 95%CI: 0.84, 3.34; P = 0.079). Trial sequential analysis (TSA) confirmed data adequacy, and meta-regression indicated that sample size, treatment duration, and patient age did not influence outcomes. JAK inhibitors are associated with an elevated risk of malignancies but do not significantly affect MACE, VTE, or DVT risk in RA patients. Further large-scale post-marketing surveillance is warranted to refine the safety profile of JAK inhibitors in RA management.