The cardiometabolic safety of dupilumab in atopic dermatitis: A global large-scale cohort study

Background: A low risk of cardiovascular and metabolic outcomes was found in the randomized clinical trials of dupilumab in atopic dermatitis (AD). Dupilumab-associated real-life long-term cardiometabolic risk relative to other systemic agents is yet to be precisely investigated. Objective: To assess the risk of cardiometabolic outcomes in patients with AD treated with dupilumab relative to those treated with methotrexate and cyclosporine. Methods: A global retrospective cohort study comprised two distinct analyses comparing patients with AD under different treatments: (i) initiators of dupilumab (n = 10,151) versus methotrexate (n = 10,151) and (ii) initiators of dupilumab (n = 6,629) versus TNFi (n = 6,629). Study groups were compared regarding the risk of 8 cardiovascular and 4 metabolic outcomes during the initial three years following drug initiation. Propensity score matching was conducted to optimize inter-group comparability. Results: Compared to methotrexate, dupilumab was associated with a decreased risk of peripheral vascular disease (PVD; hazard ratio [HR], 0.64; 95% confidence interval CI 0.45–0.90; P = 0.011), deep vein thrombosis (DVT; HR, 0.42; 95% CI, 0.26–0.69; P < 0.001), hypertension (HR, 0.67; 95% CI, 0.58–0.79; P < 0.001), type-2 diabetes mellitus (T2DM; HR, 0.53; 95% CI, 0.42–0.68; P < 0.001), and obesity (HR, 0.70; 95% CI, 0.58–0.86; P = 0.001) within the first year of treatment. Relative to cyclosporine, dupilumab conferred a lower risk of hypertension (HR, 0.52; 95% CI, 0.45–0.62; P < 0.001), hyperlipidemia (HR, 0.59; 95% CI, 0.49–0.71; P < 0.001), and T2DM (HR, 0.62; 95% CI, 0.48–0.81; P < 0.001), Conclusion: Dupilumab possesses a favorable cardiometabolic safety profile and might be preferred in patients with susceptibility and risk factors of these conditions.