Cardiovascular and thromboembolic risks of JAK inhibitors in atopic dermatitis: A global cohort study

Introduction: Janus kinase (JAK) inhibitors are increasingly used for moderate-to-severe atopic dermatitis (AD). However, concerns have emerged regarding their cardiovascular safety profile, particularly the risk of thromboembolic complications. Evidence specific to AD populations remains sparse. Objectives: To evaluate the real-world risk of myocardial infarction (MI), stroke, pulmonary embolism (PE) and deep vein thrombosis (DVT) among patients with AD treated with JAK inhibitors relative to those treated with dupilumab, methotrexate and cyclosporine. Methods: Using the TriNetX global database, we conducted three propensity score-matched analyses comparing AD patients initiating JAK inhibitors with those receiving dupilumab (n = 1006), methotrexate (n = 958) or cyclosporine (n = 948). The incidence of MI, stroke, PE and DVT over 3 years was assessed. Results: The risk of PE (hazard ratio [HR], 2.75; 95% confidence interval [CI], 1.19 to 6.38; p = 0.014) and DVT (HR, 2.54; 95% CI, 1.14 to 5.64; p = 0.017) was significantly higher among patients treated with JAK inhibitors relative to dupilumab, with a risk difference of eight and nine additional cases of PE and DVT/1000 patients starting JAK inhibitors, respectively. Relative to methotrexate, JAK inhibitors were associated with an increased risk of DVT (HR, 2.41; 95% CI, 1.14 to 5.08; p = 0.017), with a risk difference of seven additional cases/1000 patients starting JAK inhibitors. The risk of MI and stroke was not statistically elevated under JAK inhibitors in comparison to any of the comparators. Conclusions: JAK inhibitor use in patients with AD is associated with a slightly increased risk of PE and DVT compared to dupilumab and methotrexate. These findings underscore the need for careful patient selection and thrombotic risk assessment when prescribing JAK inhibitors.