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)

Abstract

Introduction & Objectives Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with comorbidities, including major adverse cardiovascular (CV) events (MACE), venous thromboembolism (VTE), and malignancy (excluding nonmelanoma skin cancer [exNMSC]). Incidence of MACE, VTE, and malignancy (exNMSC) was comparable to or lower than background rates reported in US AD population. We evaluated long-term incidence rates of MACE, VTE, and malignancy (exNMSC) by CV risk category among patients with AD with up to 6 years of UPA treatment.

Materials & Methods Data were pooled from the phase 3, randomized, double-blind, multicenter, placebo-controlled Measure Up 1 & 2 (NCT03569293, NCT03607422) and AD Up (NCT03568318) trials. AD patients were randomized 1:1:1 to once-daily oral UPA 15 mg, UPA 30 mg, or placebo. After the 16-week double-blind treatment period, patients receiving UPA continued their assigned treatment, while patients treated with placebo were rerandomized 1:1 to UPA 15 mg or 30 mg. Incidence rates for MACE (CV death, nonfatal myocardial infarction, or nonfatal stroke), VTE (deep vein thrombosis or pulmonary embolism [fatal and nonfatal]), and malignancy (exNMSC) were evaluated as exposure-adjusted incidence rates per 100 patient-years (n/100 PY). MACE, VTE, and malignancy (exNMSC) background rates in the general US AD population were assessed in a retrospective observational claims-based analysis from Optum’s deidentified Clinformatics Data Mart database; this real-world reference population included patients with an AD diagnosis during the study period (March 2017–September 2024) determined by International Classification of Diseases 9th or 10th edition codes (≥ 1 inpatient or ≥ 2 outpatient claims for AD), and age restrictions from the UPA studies (12–75 years) were implemented. Background rates were weighted to mimic the age and sex distribution in the combined UPA trial population. Cohort stratification was based on the presence of CV risk factors at baseline (0 vs ≥ 1); UPA phase 3 data were further stratified by 1 vs 2 CV risk factors. CV risk factors included prior CV event, hypertension, diabetes mellitus, tobacco/nicotine use (current and former), elevated low-density lipoprotein cholesterol, or lowered high-density lipoprotein cholesterol.

Results 2683 UPA-treated patients were included (UPA 15 mg, n = 1337, PY = 4435.2; UPA 30 mg, n = 1346, PY = 4752.5). MACE, VTE, and malignancy (exNMSC) background rates from the claims-based study were evaluated in 50,447 patients with AD. Long-term incidence rates in patients with up to 6 years of UPA treatment were low for MACE and VTE (all ≤ 0.2 n/100 PY) and malignancy (exNMSC; all ≤ 0.7 n/100 PY) and similar for patients who had 0 vs ≥ 1 CV risk factor. Rates from UPA phase 3 studies were similar to real-world US incidence rates in patients with AD. Rates remained low when UPA-treated patients were stratified by 1 vs 2 CV risk factors.

Conclusion Incidence rates of MACE, VTE, and malignancy (exNMSC) in patients with moderate-to-severe AD who received up to 6 years of UPA treatment remained low and consistent with those observed in the overall population of patients with AD, regardless of CV risk category.