Is Upadacitinib Cardioprotective in Chronic Inflammatory Diseases? A Review of Major Adverse Cardiovascular Events and Venous Thromboembolism in Atopic Dermatitis
May 2025 | Volume 24 | Issue 5 | 530 | Copyright © May 2025
Published online April 28, 2025
Omar Alani ScBa, David Wang b, Samer Wahood BAc, Sabine Obagi BAd, Diego Dasilva MDe, Matthew J. Zirwas MDf, Fabrizio Galimberti MD PhDg, Christopher G. Bunick MD PhDh
aDepartment of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY
bDepartment of Dermatology, Boston University Chobanian and Avedisian School of Medicine, Boston, MA
cDepartment of Dermatology, The Warren Alpert Medical School of Brown University, Providence, RI
dDivision of Dermatology, University of Arizona College of Medicine, Tucson, Arizona
eForefront Dermatology & Eastern Virginia Medical School, Virginia Beach, VA
fDOCS Dermatology, Bexley, OH
gDepartment of Dermatology, Conway Medical Center Conway, SC
hDepartment of Dermatology and Program in Translational Biomedicine, Yale School of Medicine, New Haven, CT
Abstract
Background: Atopic dermatitis (AD) is a chronic inflammatory skin condition associated with risk of cardiovascular disease (CVD), potentially mediated by persistent systemic inflammation. Upadacitinib (UPA), a selective Janus kinase 1 (JAK1) inhibitor, effectively reduces AD-related inflammation and may confer additional cardioprotective and thromboprotective benefits.
Objective: This review evaluates the incidence of major adverse cardiovascular events (MACE) in patients with AD, comparing background rates reported in the literature to long-term MACE rates observed in clinical trials of UPA.
Methods: A literature review was conducted across PubMed, SCOPUS, and EMBASE to identify studies reporting MACE and venous thromboembolism (VTE) rates in moderate-to-severe AD populations. Long-term (5-year) incidence rates in UPA-treated patients were extracted from clinical trials. Reported background incidence rates in AD populations were included.
Results: MACE rates in the background AD populations ranged from 0.3 to 1.2 per 100 patient-years (PY), whereas UPA-treated patients exhibited lower rates (15 mg: 0.2, 30 mg: <0.1). VTE rates in AD populations ranged from 0.1 to 0.3, while UPA-treated patients showed lower rates at 0.1 for both 15 mg and 30 mg doses.
Conclusions: The observed lower MACE and VTE rates in UPA-treated patients suggests potential cardiovascular and thrombotic benefits. While these findings are hypothesis-generating, further studies are needed to confirm the impact of UPA on CVD and thrombosis and explore the mechanistic basis of JAK1 inhibition in cardiovascular health.
Citation: Alani O, Wang D, Wahood S, et al. Is upadacitinib cardioprotective in chronic inflammatory diseases? A review of major adverse cardiovascular events and venous thromboembolism in atopic dermatitis. J Drugs Dermatol. 2025;24(5):doi:10.36849/JDD.9049
INTRODUCTION
Atopic dermatitis (AD) is a chronic inflammatory skin condition characterized by recurrent eczematous lesions and pruritus.1 Beyond its significant impact on patient quality of life, its systemic inflammatory nature may predispose patients to an increased risk of cardiovascular diseases (CVD) along with pulmonary embolism and deep venous thrombosis.2,3 This parallels observations in other chronic inflammatory diseases, including psoriasis and rheumatoid arthritis, where heightened cardiovascular and thrombotic risk have been well-documented, showing increased rates of major adverse cardiovascular events (MACE) and venous thromboembolism (VTE).3,4 Incidences of MACE, such as myocardial infarction and stroke, serve as measurable and clinically significant outcomes for assessing the risk of CVD in patients with chronic inflammatory diseases.5 Additionally, incidence of VTE, which includes pulmonary emboli and deep venous thrombosis, serves as a measure of thrombotic risk in inflammatory conditions.
Upadacitinib (UPA), a selective Janus kinase 1 (JAK1) inhibitor, has emerged as a highly effective treatment option for moderate-to-severe AD, modulating key inflammatory pathways.6 UPA is FDA-approved for eight immune-mediated inflammatory disorders--rheumatoid arthritis, psoriatic arthritis, polyarticular juvenile idiopathic arthritis, AD, ulcerative colitis, Crohn’s disease, ankylosing spondylitis, and non-radiographic axial spondylarthritis—and is currently being studied for alopecia areata, vitiligo, and hidradenitis suppurativa. Clinical trials in AD
