| Summary: | Background: We aimed to systematically assess a possible association of tofacitinib therapy with cardiovascular events (CVEs) and all-cause mortality. Methods: Systematic searches of PubMed, Embase, and Cochrane Library were conducted from inception through March 2019. Randomized controlled trials in patients with immune-mediated inflammatory diseases (IMIDs) reporting safety data were included. Included studies compared tofacitinib with placebo or 5 mg tofacitinib with 10 mg tofacitinib. The primary and secondary outcome measures were all CVEs [major adverse cardiovascular events (MACEs)/venous thromboembolism events (VTEs)] and all-cause mortality. Results: 29 studies randomizing 13,611 patients were included. Compared with placebo, there was no significant increased risk of all CVEs (OR = 1.07, 95% CI 0.49–2.34), MACEs (OR 1.54, 95% CI 0.42–5.59), or all-cause mortality (OR = 1.13, 95% CI 0.26–4.95), but a decreased rate of VTEs (OR 0.03, 95% CI 0.00–0.21) in patients with IMIDs initiating tofacitinib. Meanwhile, paired comparison showed 10 mg tofacitinib twice daily was associated with a significantly lower incidence of all CVEs (OR = 0.56, 95% CI 0.33–0.96), MACEs (OR = 0.48, 95% CI 0.22–1.05), or all-cause mortality (OR = 0.47, 95% CI 0.19–1.17), but a trend toward an increase in VTEs risk (OR = 1.47, 95% CI 0.25–8.50), compared with the 5 mg regimen. Conclusion: Compared with placebo, there was no augmented risk of CVEs and all-cause mortality in patients with IMIDs following tofacitinib treatment in a short-term perspective, whereas 10 mg twice daily tofacitinib appeared to be associated with reduction in cardiovascular and all-cause mortality risks, except VTEs, relative to the 5 mg twice daily dose. Long-term studies and postmarketing risk monitoring are increasingly needed to develop a better understanding.
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