Dupilumab Cardiometabolic Safety in Real-World Study of Atopic Dermatitis Supports Clinical Trial Evidence

Dupilumab may be associated with a reduced risk of cardiometabolic conditions compared with methotrexate and cyclosporine in patients with atopic dermatitis (AD), suggest findings from a recent population-based, retrospective cohort study.1

Specifically, the study revealed reduced risk of peripheral vascular disease (PAD), deep vein thrombosis (CVT), hypertension, type 2 diabetes (T2D), obesity and hyperlipidemia within the first year of treatment among adults treated with dupilumab compared with both other systemic medications.1

The global study, published in the Archives of Dermatologic Research, used real-world data from the TriNetX database to analyze initiators of dupilumab (n = 10,151) vs methotrexate (n = 10,151) and initiators of dupilumab (n = 6,629) vs cyclosporine (n = 6,629). Mean age in the first matched cohort was 41.7 years and slightly older in the second, at 49.2 years. Approximately one-third of participants were men across the 4 treatment groups.1

Authors, led by Khalaf Kridin, MD, PhD, of the department of dermatology at University of Lübeck, in Lübeck, Germany, compared the 2 groups for risk of 8 cardiovascular and 4 metabolic outcomes, using propensity score matching to balance participant characteristics between groups. They reported comparative risk at 1 year after initiation and up to 3 years.

Findings1

Methotrexate. In the comparison of dupilumab with methotrexate initiators, study authors reported a significantly reduced risk of 36% for PAD (95% CI, 0.45-0.90; P =.011), of 58% for DVT (95% CI, 0.26-0.69; P < .001), of 33% for hypertension (HR, 0.67; 95% CI, 0.58-0.79; P <.001), of 47% for T2D (HR, 0.53; 95% CI, 0.42-0.68; P <.001), and of 30% for obesity (HR, 0.70; 95% CI, 0.58-0.86; P =.001). The reduced risk of hypertension among participants treated with dupilumab was durable for 1 to 3 years after treatment initiation (HR, 0.73; 95% CI, 0.61-0.89; P =.001), according to the study.

Cyclosporine. Reporting on the second analysis of 6629 matched pairs initiating treatment with either dupilumab or cyclosporine, the investigators found the former associated with a significant 35% lower risk of congestive heart failure (HR, 0.65; 95% CI, 0.48-0.89; P =.007), a 48% reduced risk of hypertension (HR, 0.52; 95% CI, 0.45-0.62; P <.001), 42% lower risk for hyperlipidemia (HR, 0.59; 95% CI, 0.49-0.71; P <.001), and a 38% lower risk of T2D (HR, 0.62; 95% CI, 0.48-0.81; P <.001) within the first 52 weeks of treatment. They also found persistent cardiometabolic benefits for dupilumab vs cyclosporine from 1 to 3 years after treatment began, with reduced risk for:

• PAD 44% (HR, 0.56; 95% CI, 0.38-0.82; P =.002)
• Hypertension 25% (HR, 0.75; 95% CI, 0.60-0.94; P =.011)
• Hyperlipidemia 40% (HR, 0.60; 95% CI, 0.48-0.75; P < .001)
• T2D 31% (HR, 0.69; 95% CI, 0.51-0.69; P = .024)

Existing literature on comorbidities associated with AD clearly demonstrates increased risk for other atopic diseases, including vitiligo, alopecia areata, rheumatoid arthritis and inflammatory bowel disease.2 Some research on cardiovascular outcomes has found significant associations with AD with the risk increasing with AD severity but also points to considerable between-study heterogeneity.2 Other studies report a “modest association.”3

The current analyses of real-world data support findings from pivotal clinical trials of dupilumab that showed a low risk of cardiometabolic outcomes in adults with AD. The authors acknowledge limitations associated with the study, however, including dependence on electronic health record data as well as the inability to control for the severity of AD and participants’ clinical characteristics.1

“The current study further substantiates the highly favorable cardiometabolic safety profile of dupilumab that has already emerged in RCTs,” the authors concluded. They noted that dupilumab may be a preferable option for AD patients with pre-existing or high-risk cardiovascular and metabolic conditions.1

References
1. Kridin K, Abdelghaffar M, Ludwig RJ. The cardiometabolic safety of dupilumab in atopic dermatitis: a global large‑scale cohort study. Arch Dermatol Res. 2025;317(1):296. doi:10.1007/s00403-024-03601-0
2. Ascott A, Mulick A, Yu A, et al.Atopic eczema and major cardiovascular outcomes: A systematic review and meta-analysis of population-based studies. J Allergy Clin Immunol. 2019 May;143(5):1821–1829. doi: 10.1016/j.jaci.2018.11.030
3. Standl M, Tesch F, Baurecht H, et al. Association of atopic dermatitis with cardiovascular risk factors and diseases. J Investigative Derm. 2017;137(5):1074-1081. doi:org/10.1016/j.jid.2016.11.031