New research presented at the 2025 European Academy of Dermatology and Venereology (EADV) Congress in Paris, France, provides compelling real-world evidence about the safety of upadacitinib (Rinvoq, AbbVie) when it comes to long-term incidence rates of major adverse cardiovascular events (MACE), venous thromboembolism (VTE), and malignancy (excluding non-melanoma skin cancers (NMSC)).
The main takeaway? MACE, VTE, and malignancy (excluding NMSC) incidence rates among patients with moderate-to-severe atopic dermatitis (AD) who received up to six years of upadacitinib treatment were low, regardless of whether they had any baseline cardiovascular (CV) risk factors or the number of CV risk factors. In addition, there was no evidence of a dose-dependent pattern. These rates are consistent with those observed in the real-world population of patients with AD in the United States.
Christopher Bunick, MD, PhD, an Associate Professor of Dermatology at Yale University in New Haven, CT, and Director of the Bunick Lab at Yale, presented the findings on podium. He chatted with The Dermatology DigestÒ on the new findings and their implications for patient care.
TDD: What is the main takeaway here regarding upadacitinib and MACE, VTE, and cancer?
Christopher Bunick, MD, PhD: “Across multi-year (up to 6 years) follow-up in upadacitinib Phase 3 trials, adjudicated rates of major adverse cardiovascular events (MACE), venous thromboembolism (VTE), and malignancy, excluding non-melanoma skin cancer (NMSC), were very low. These rates were consistent whether or not patients had baseline cardiovascular risk factors, such as hypertension, hyperlipidemia, diabetes, or smoking history, and were comparable to or below background rates reported for atopic dermatitis in real-world cohorts. Importantly, there was no evidence of a dose-dependent pattern, as results were similar for both 15mg and 30mg. Together, this supports a favorable benefit risk profile for upadacitinib 15mg and 30mg in adolescents and adults with moderate-to-severe AD.”
TDD: Have the safety concerns been adequately addressed?
Dr. Bunick: “Yes. This analysis provides strong reassurance by directly evaluating MACE, VTE, and malignancy with adjudicated endpoints, long-term follow-up, and stratification by cardiovascular risk. The findings were consistent across risk strata, and the rates were comparable to or below background in real-world AD populations. Furthermore, these results align with several real-world database epidemiological studies showing no meaningful differences between JAK inhibitors and interleukin (IL) 4/IL 13 biologics in the risks of MACE, VTE, or malignancy. As with all medicines, there are benefits and risks, and U.S. Food and Drug Administration (FDA) approvals reflect that the benefits outweigh the risks for indicated patients; in many cases, the risk of not treating uncontrolled disease is higher than the risk of treating.”
TDD: Is it possible that upadacitinib is actually cardioprotective?
Dr. Bunick: There is an emerging scientific rationale that upadacitinib may be cardioprotective, which I view as hypothesis-generating rather than proven. JAK1 inhibition reduces systemic inflammatory mediators linked to atherosclerosis and thrombosis, with observed reductions in C-reactive protein (CRP) and indirect downmodulation of IL-6 and interferon gamma, as well as evidence of decreased endothelial prothrombotic activation and leukocyte endothelial adhesion. Together, these observations support a biologically plausible pathway for cardiovascular and thrombotic benefit, but confirmation will require dedicated outcomes studies.”
