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Presentation

JAK Inhibitors, Systemic Inflammation, and Cardiovascular Risk in Dermatologic Disease

Description

The speaker argues that JAK inhibitors and other advanced dermatologic therapies should be viewed through the lens of systemic inflammation and cardiovascular risk, not just skin efficacy. He reviews concerns from the oral surveillance study, noting its limitations (open-label design, heavy background immunosuppression, older high-risk rheumatoid arthritis population, high discontinuation, and no placebo arm) and cautions against overgeneralizing its results. A major theme is that chronic systemic corticosteroid use is harmful and should generally be avoided beyond 3 to 4 weeks, since even short courses can raise risks of sepsis, venous thromboembolism, and fracture. He also emphasizes that atopic dermatitis and psoriasis are both associated with subclinical atherosclerosis and elevated inflammatory biomarkers such as hs-CRP, suggesting these diseases themselves contribute to cardiovascular risk. The talk contrasts different JAK inhibitors by selectivity, metabolites, and clinical safety patterns, highlighting that they are not interchangeable and that drug choice should consider cardiovascular history and other patient factors. Data presented suggest that in patients without atherosclerosis, MACE differences seen in oral surveillance largely disappear, implying baseline vascular disease may be the key driver rather than the drug alone. He also discusses weight gain and metabolic effects, especially with stronger JAK2 inhibition, and notes that JAK inhibitor and biologic safety profiles for MACE, VTE, and malignancy may be more similar than many assume. Overall, he concludes that treating systemic inflammation can lower inflammatory and cardiovascular biomarkers, and that JAK inhibitors may ultimately have neutral or possibly protective cardiovascular effects, though careful patient counseling remains essential.

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Conclusions

The presentation argues that the cardiovascular and cancer risks seen with JAK inhibitors are strongly influenced by patient baseline atherosclerosis and inflammatory burden rather than by the drugs alone.
It concludes that oral surveillance had important design limitations, so its findings should not be interpreted as proving that tofacitinib uniquely drives excess MACE or malignancy risk.
The talk concludes that systemic corticosteroids should be avoided whenever possible in inflammatory skin disease and, if used at all, should be restricted to very short courses before transition to steroid-sparing therapy.
It concludes that even short courses of oral corticosteroids can increase risks such as sepsis, VTE, and fracture, making them poor routine options for atopic dermatitis.
The presentation concludes that psoriasis and atopic dermatitis are both linked to subclinical atherosclerosis and therefore should be viewed as systemic inflammatory diseases with cardiovascular implications.
It concludes that atopic dermatitis has meaningful molecular overlap with psoriasis and can involve Th1, Th22, and Th17 pathways rather than being purely a Th2 disease.
The talk concludes that treating systemic inflammation in AD can reduce biomarkers associated with cardiovascular risk, suggesting potential downstream cardiovascular benefit.
It concludes that JAK inhibitors are not a single class with identical safety or biology, and that selectivity, metabolism, and off-target effects matter.
The presentation concludes that upadacitinib and some other modern JAK inhibitors show long-term safety rates for MACE, VTE, and malignancy that are comparable to or below background AD population rates.
It concludes that in the available data, JAK inhibitor safety appears broadly comparable to tralokinumab rather than clearly worse than biologic therapy.
The presentation concludes that upadacitinib lowers systemic inflammatory biomarkers such as hs-CRP and eosinophils, supporting a real systemic anti-inflammatory effect.
It concludes that JAK inhibition may even have cardiovascularly protective potential, though this remains a hypothesis that requires further study.

Gelfand JM, Song WB, Langan SM, Garnick MS. "Cardiodermatology: the heart of the connection between the skin and cardiovascular disease." Nat Rev Cardiol. 2025 May;22(5):354-371.#10.1038/s41569-024-01097-9
Bunick et al., presented Winter Clinical Hawaii, Jan 2026.