Cardiovascular Safety Observed in Upadacitinib Over 6 Years for Atopic Dermatitis

Treatment of atopic dermatitis over 6 years results in comparable cardiovascular risk to that of the overall population of patients with atopic dermatitis, new data suggest, regardless of one’s cardiovascular risk category.1

These late-breaking data, highlighted at the European Academy of Dermatology and Venereology (EADV) 2025 Congress in Paris, were presented by investigator Christopher G. Bunick, MD, PhD, from the Yale School of Medicine. Bunick and his team noted that atopic dermatitis, a chronic inflammatory skin disease, is sometimes accompanied by comorbidities such as major adverse cardiovascular events (MACE), venous thromboembolism (VTE), and malignancies other than nonmelanoma skin cancer (exNMSC).

This medication was approved by the US Food and Drug Administration (FDA) in 2022 for the treatment of patients 12 years of age and older with atopic dermatitis.1 Although a previous integrated safety analysis of phase 3 clinical research had assessed patients with moderate-to-severe atopic dermatitis on the Janus kinase (JAK) inhibitor upadacitinib for as long as 6 years, a new analysis was deemed as necessary.

The prior data suggested that MACE, VTE, and malignancy (exNMSC) risk had been comparable to—or in some cases lower than—the background rates observed in the general US population with atopic dermatitis. In the current analysis, however, Bunick et al looked into patients' long-term incidence rates of these same cardiovascular outcomes stratified specifically by cardiovascular risk status in those treated with upadacitinib for up to 6 years.

Their pooled data resulted from a set of three phase 3 randomized, double-blind, multi-center, placebo-controlled studies: Measure Up 1 (NCT03569293), Measure Up 2 (NCT03607422), and AD Up (NCT03568318). Participants in these studies were randomized in equal proportions to once-per-day upadacitinib 15 mg, 30 mg, or placebo.

After a 16-week blinded treatment period, Bunick and colleagues had patients who initially were assigned to upadacitinib continue their regimen, whereas subjects given the placebo were re-randomized to either dose of the drug. They expressed rates for MACE (defined as cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke), VTE (deep vein thrombosis or pulmonary embolism, including fatal and non-fatal events), and exNMSC as exposure-adjusted incidence rates per 100 patient-years (n/100 PY).

Background rates of these events in the general US population with atopic dermatitis, for the sake of comparison, were derived from a retrospective claims-based analysis via Optum’s deidentified Clinformatics Data Mart database. In this reference cohort, participants with at least a single inpatient or 2 outpatient claims between March 2017 - September 2024 were included. They were also restricted to ages 12–75 years to match the trial populations.

Background incidence rates among subjects were weighted by Bunick and coauthors to reflect the sex and age distribution of the pooled upadacitinib trial population. They stratified patients by baseline cardiovascular risk (0 vs ≥1 risk factor). The team also subdivided upadacitinib-treated participants by the existence of 1 versus 2 risk factors.

In their final analysis, 2683 upadacitinib-treated individuals were included (UPA 15 mg: n = 1337, PY = 4435.2; UPA 30 mg: n = 1,346, PY = 4752.5). The study's claims-based reference population was made up of 50,447 individuals living with this skin condition. Across up to 6 years of treatment, the drug was linked with consistently low incidence rates of VTE and MACE (each ≤ 0.2 n/100 PY) as well as malignancy excluding NMSC (≤ 0.7 n/100 PY).1

Overall, Bunick and colleagues concluded that rates of MACE, malignancy excluding nonmelanoma skin cancer (exNMSC), and VTE, were comparable to those of the general atopic dermatitis population, regardless of cardiovascular risk.

References

1. Bunick C, Stein Gold L, Silverberg J, et al. Patients with Cardiovascular Risk Factors and Atopic Dermatitis: Long-Term Safety of Upadacitinib for Major Adverse Cardiovascular Events, Venous Thromboembolism, or Malignancy (Excluding Nonmelanoma Skin Cancer). Presented at the 2025 European Academy of Dermatology and Venereology (EADV) Congress, Sept 17-20, 2025.

2. Butera A. FDA Approves Upadacitinib for Patients 12 Years and Older with Moderate to Severe Atopic Dermatitis. HCPLive. January 14, 2022. Accessed September 19, 2025. https://www.hcplive.com/view/fda-upadacitinib-children-atopic-dermatitis.