Long-Term Data Reinforce Safety of Upadacitinib in Treating Atopic Dermatitis in Oral Contraceptive Users 

Women with atopic dermatitis (AD) who take oral contraceptive pills (OCPs) need not write off upadacitinib as a treatment option, according to pooled data from several phase 3 randomized clinical trials, which revealed a favorable benefit–risk profile of the Janus kinase (JAK) inhibitor in this population. 

Individuals living with atopic dermatitis experience chronic inflammation, which may increase their risk for comorbid conditions, including cardiovascular disease and certain malignancies (Thyssen JP et al. J Allergy Clin Immunol 2023;151:1155–62). While JAK inhibitors have emerged as promising options for the long-term control of AD symptoms and the prevention of disease flares, concerns remain about the potential adverse events associated with these therapies, especially in the context of coexisting risk factors. Upadacitinib, an oral selective JAK inhibitor approved for the treatment of moderate to severe AD in adolescents and adults, demonstrated a favorable benefit-risk profile and sustained efficacy responses through 52 weeks in the phase 3, randomized, placebo-controlled trials Measure Up 1 and Measure Up 2. The studies included a total of 1609 patients with AD aged 12 to 75 years, who were randomized to receive either once-daily orally administered upadacitinib 15 mg, upadacitinib 30 mg, or placebo as a monotherapy. In the AD Up phase 3 trial, 901 patients were randomly assigned to receive upadacitinib 15 mg or 30 mg plus topical corticosteroids, or placebo plus topical corticosteroids. Safety data up to 6 years of treatment collected from all three studies showed that the incidence rates of major adverse cardiovascular events (MACE), venous thromboembolism (VTE), and malignancy (excluding nonmelanoma skin cancer) were similar to or lower than the real-world rates reported in patients with AD living in the United States. MACE included cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, whereas VTE was defined as deep vein thrombosis or pulmonary embolism. 

In an analysis presented at the 2025 Fall Clinical Dermatology Conference, researchers compared the incidence rates of MACE, VTE, and malignancy of 1,178 women treated with upadacitinib for up to 6 years in the three studies with those of more than 22,000 U.S.-based women with a diagnosis of AD between March 2017 and September 2024, who were designated as the real-world reference population. Because OCP use is a known risk factor for cardiovascular events, the data were stratified by OCP use in both cohorts. 

Women treated with upadacitinib long-term had low incidence of MACE, VTE, and malignancy (excluding nonmelanoma skin cancer), regardless of OCP use. While upadacitinib-treated patients who used OCPs had no MACE or VTE events, the malignancy incidence rates from the phase 3 studies mirrored the real-world incidence rates reported in female patients with AD in the United States. Moreover, OCP users had similar or more favorable cardiovascular risk profiles compared with women who did not use OCPs, suggesting that contraceptive use did not independently increase long-term cardiovascular risk when combined with upadacitinib. 

“Together, these results support the favorable benefit-risk profile of upadacitinib 15 mg and upadacitinib 30 mg for the treatment of moderate to-severe atopic dermatitis in females of childbearing potential who use OCPs,” the investigators noted. While the data continue to emerge, providers can help patients understand the risks and benefits associated with JAK inhibitors and optimize treatment plans.