Understanding the Safety Profile of Oral JAK Inhibitors in Atopic Dermatitis

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Oral JAK inhibitors demonstrate an extensive safety profile across multiple age groups and indications, with upadacitinib approved for use in patients as young as 2 years for juvenile idiopathic arthritis and in older populations (mean age, 71 years) for giant cell arteritis. Despite FDA boxed warnings applied to all JAK inhibitors, comprehensive safety analyses of more than 9000 patient-years reveal that only herpes zoster reactivation, tuberculosis, and nonmelanoma skin cancer show statistically significant increased rates across all 9 approved indications.

Emerging evidence suggests potential cardioprotective benefits of JAK inhibitors in patients with atopic dermatitis. Recent analyses demonstrate that patients with atopic dermatitis who are on JAK inhibitors have lower rates of major adverse cardiovascular events (MACEs) and venous thromboembolism (VTE) compared with both the general population and patients with untreated atopic dermatitis. This cardioprotective effect likely stems from the systemic anti-inflammatory properties of JAK inhibitors, addressing the underlying inflammatory burden that contributes to cardiovascular risk in atopic dermatitis.

Multiple targeted safety studies have addressed specific concerns, including analyses of JAK inhibitor use in women on oral contraceptives (showing no increased VTE risk), smokers (no increased MACEs, VTE, or malignancy risk), and geriatric populations (no increased adverse events). The most common manageable adverse effects include mild acne (approximately 10% of patients) and the need for routine monitoring, including annual skin cancer surveillance, shingles vaccination, and tuberculosis screening with QuantiFERON testing.