Six-Year Upadacitinib Safety Data Shows Comparable Cardiovascular Risk in Atopic Dermatitis Patients
核心洞察
New 6-year safety data for upadacitinib in atopic dermatitis (搜索) patients shows cardiovascular risk comparable to the general population with the condition, regardless of baseline cardiovascular risk factors.
The analysis of 2,683 patients from three phase 3 trials demonstrated consistently low incidence rates of major adverse cardiovascular events (搜索), venous thromboembolism (搜索), and malignancies (搜索) over the extended treatment period.
Upadacitinib maintained a stable safety profile with no new safety signals emerging compared to earlier reports, providing reassurance for long-term JAK inhibitor (搜索) use in dermatology.
Long-term safety data for upadacitinib in atopic dermatitis (搜索) patients demonstrates cardiovascular risk profiles comparable to the general population with the condition, according to new 6-year analysis presented at the European Academy of Dermatology and Venereology (EADV) 2025 Congress in Paris.
The comprehensive safety analysis, led by Christopher G. Bunick, MD, PhD, from Yale School of Medicine, examined cardiovascular outcomes in patients treated with the Janus kinase (搜索) (JAK) inhibitor for up to six years, representing one of the longest datasets available for JAK inhibitors in dermatology.
Comprehensive Phase 3 Trial Analysis
The pooled analysis drew from three phase 3 randomized, double-blind, multi-center, placebo-controlled studies: Measure Up 1 (NCT03569293), Measure Up 2 (NCT03607422), and AD Up (NCT03568318). A total of 2,683 upadacitinib-treated individuals were included in the final analysis, with 1,337 patients receiving 15 mg daily and 1,346 patients receiving 30 mg daily.
Participants were initially randomized in equal proportions to once-daily upadacitinib 15 mg, 30 mg, or placebo. After a 16-week blinded treatment period, patients originally assigned to upadacitinib continued their regimen, while those given placebo were re-randomized to either dose of the drug.
Cardiovascular Risk Stratification Results
The researchers evaluated rates of major adverse cardiovascular events (搜索) (MACE), defined as cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke, along with venous thromboembolism (搜索) (VTE) and malignancies (搜索) excluding nonmelanoma skin cancer (exNMSC). These outcomes were expressed as exposure-adjusted incidence rates per 100 patient-years.
Background rates for comparison were derived from a retrospective claims-based analysis using Optum's deidentified Clinformatics Data Mart database, which included 50,447 individuals with atopic dermatitis (搜索) aged 12-75 years. The background incidence rates were weighted to reflect the sex and age distribution of the pooled upadacitinib trial population.
Across up to six years of treatment, upadacitinib demonstrated consistently low incidence rates of VTE and MACE (each ≤ 0.2 per 100 patient-years) as well as malignancy excluding nonmelanoma skin cancer (≤ 0.7 per 100 patient-years). These rates remained comparable to those observed in the general atopic dermatitis (搜索) population, regardless of patients' baseline cardiovascular risk status.
Long-Term Safety Profile Confirmation
The analysis revealed no new safety signals compared to earlier reports, with adverse events such as acne, upper respiratory infections, and laboratory abnormalities remaining consistent with prior data and showing no progression with extended treatment duration.
"I had the privilege of presenting a late breaking presentation on the safety of upadacitinib. Now, this was a particularly unique study because it involved a couple different things. First, it was looking at 6-year safety data," Bunick explained during the presentation.
The findings address ongoing concerns surrounding JAK inhibitors and their long-term tolerability, particularly regarding malignancy, cardiovascular risk, and serious infections. As Bunick noted, the results "really provided reassurance to dermatologists that long-term use of upadacitinib continues to be safe and manageable."
Clinical Implications for Treatment Decisions
The study's multinational cohort reflects real-world clinical diversity, allowing clinicians to better understand upadacitinib's applicability across different patient populations. For clinicians managing atopic dermatitis (搜索) and other inflammatory skin diseases, these findings contribute to the ongoing evaluation of benefit-risk balance.
Upadacitinib, approved by the FDA in 2022 for patients 12 years and older with atopic dermatitis (搜索), remains an effective option for patients with moderate-to-severe disease who may have limited alternatives. The 6-year safety update provides further evidence supporting its long-term use in dermatology, with clinicians advised to continue individualizing therapy and monitoring for known adverse effects when making treatment decisions for chronic inflammatory skin conditions.