Upadacitinib Safe for Up to 6 Years for Atopic Dermatitis, Regardless of Smoking History

Individuals with moderate-to-severe atopic dermatitis and a history of cigarette-smoking who were treated with upadacitinib (RINVOQ) for up to 6 years had comparable incidence rates of major adverse cardiovascular events (MACE), venous thromboembolism (VTE), and malignancy (excluding non-melanoma skin cancer) to those observed in a real-world population of people living with atopic dermatitis, new data suggest.1

These data were the result of a recent study presented at the 2025 Revolutionizing Atopic Dermatitis (RAD) Conference.1 The study authors included such investigators as Naiem Issa, MD, PhD, a board-certified dermatologist at Forefront Dermatology. Issa et al highlighted atopic dermatitis as a persistent inflammatory condition linked to various complications such as VTE, MACE, and different forms of cancer (excluding nonmelanoma skin cancer or NMSC).

The investigators pointed to a pooled safety analysis from phase 3 clinical trials on upadacitinib, the results of which had demonstrated that rates of VTE, MACE, and malignancy in those with moderate-to-severe atopic dermatitis who were treated for up to 6 years with the drug were similar to—or even lower than—rates observed in the general population with the same skin condition. They sought in the current analysis to explore smoking history as a risk factor.

The long-term incidence of these events in those with moderate-to-severe atopic dermatitis treated with upadacitinib was assessed by Issa and coauthors, with participants being stratified by their smoking status at the point of baseline. The group included current/former smokers and compared them to ‘never smokers.’

Data in the investigators’ analysis were drawn from 3 randomized, multicenter, double-blind, placebo-controlled phase 3 studies: Measure Up 1 and 2 (NCT03569293, NCT03607422) and AD Up (NCT03568318).2,3 Adolescents and adults aged 12 to 75 years were included as subjects in these 3 studies, and they were randomized in a 1:1:1 ratio to be given oral upadacitinib at 15 mg, at 30 mg, or a placebo.

Throughout the Measure Up 1 and 2 studies, treatment was provided as monotherapy, whereas in the AD Up analysis, upadacitinib had been administered alongside topical corticosteroids. After the initial 16-week treatment period, patients on placebo were re-randomized to receive either UPA 15 mg or 30 mg, while those being given upadacitinib carried on with their assigned dose.

Issa and colleagues looked at rates of MACE, which was defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. They also looked at VTE, defined either as pulmonary embolism or deep vein thrombosis. Additionally, malignancies excluding NMSC were assessed. All of these were measured via exposure-adjusted incidence rates (EAIRs) per 100 patient-years (n/100 PY).

Comparisons with these outcomes were made to baseline rates in the general population of US patients with atopic dermatitis, with information on these patients being derived from a retrospective claims-based analysis of the Optum Clinformatics Data Mart. The investigators’ reference population would involve 50,447 individuals aged 12–75 years diagnosed with the skin disease between March 2017 - September 2024.

Those involved would be required to have either ≥1 inpatient or ≥2 outpatient atopic dermatitis claims. Issa et al statistically weighted the age and sex distribution of this reference group to match that of the upadacitinib phase 3 trial population.

Overall, the investigative team had included 2,683 participants from the upadacitinib trials in their safety analysis. Specifically, there were 1,337 in the 15 mg arm and 1,346 in the 30 mg arm. Among both the smoker and nonsmoker cohorts in this analysis who had been treated with the medication, VTE incidence was shown to be ≤0.2 per 100 PY, MACE incidence was shown to be ≤0.3 events per 100 PY, and malignancy incidence (not including NMSC) was shown to be ≤0.7 per 100 PY.1

“Among patients with moderate-to-severe [atopic dermatitis] who received [upadacitinib] treatment for up to 6 years, incidence rates of MACE, VTE, and malignancy (excluding NMSC) were low,” the investigators concluded.1 “These rates were lower than or consistent with background rates observed in a real-world population of patients with [atopic dermatitis], regardless of smoking history.”

For any additional information on this topic or related topics in the atopic dermatitis space, including late-breaking data, view the latest conference coverage.

References

1. Issa N, Stein Gold L, Guttman-Yassky E, et al. Patients with a Smoking History and Atopic Dermatitis: Long-Term Safety of Upadacitinib for MACE, VTE and Malignancy. Poster presented at: 2025 Revolutionizing Atopic Dermatitis Conference; June 6-7, 2025; Nashville, TN.

2. Irvine A, Silverberg J, Pechonkina A, et al. Efficacy and Safety of Upadacitinib Through 188 Weeks in Adolescents and Adults with Moderate-to-Severe Atopic Dermatitis: Phase 3 Randomized Clinical Trial Results. Presented as part of the 2024 Revolutionizing Atopic Dermatitis Mid-Year Virtual Update. December 8, 2024. Accessed June 12, 2025.

3. Stein Gold L, Shahriari M, Guttman-Yassky E, et al. Patients with Atopic Dermatitis Using Oral Contraceptive Pills or Hormone Replacement Therapy: Long-Term Safety of Upadacitinib for Major Adverse Cardiovascular Events, Venous Thromboembolism, or Malignancy (Excluding Nonmelanoma Skin Cancer). Poster presented at: 2025 Revolutionizing Atopic Dermatitis Conference; June 6-7, 2025; Nashville, TN.