Patients With Atopic Dermatitis Using Oral Contraceptive Pills or Hormone Replacement Therapy: Long-Term Safety of Upadacitinib for Major Adverse Cardiovascular Events, Venous Thromboembolism, or Malignancy (Excluding Nonmelanoma Skin Cancer)

Abstract

Introduction & Objectives Long-term incidence rates of major adverse cardiovascular events (MACE), venous thromboembolism (VTE), and malignancy (excluding nonmelanoma skin cancer [exNMSC]) according to baseline oral contraceptive pill (OCP) and hormone replacement therapy (HRT) use were assessed among patients with moderate-to-severe Atopic Dermatitis (AD) with up to 6 years of upadacitinib (UPA) treatment.

Materials & Methods This analysis evaluated pooled data from the randomized, double-blind, multicenter, placebo-controlled, phase 3 Measure Up 1/2 (NCT03569293/NCT03607422) and AD Up (NCT03568318) studies. Patients with moderate-to-severe AD (aged 12–75 years) were randomized 1:1:1 to receive once-daily oral UPA 15 mg, UPA 30 mg, or placebo as monotherapy (Measure Up 1/2) or with concomitant topical corticosteroids (AD Up) for 16 weeks. At week 16, patients receiving placebo were rerandomized 1:1 to UPA 15 mg or 30 mg, while patients initially randomized to UPA continued their assigned treatment. Incidence of MACE, VTE, and malignancy (exNMSC) was reported as exposure-adjusted incidence rates per 100 patient-years (n/100PY). For context, background rates of MACE, VTE, and malignancy (exNMSC) in the general US AD population were assessed in a retrospective observational claims-based analysis from Optum’s deidentified Clinformatics Data Mart database; this analysis included females who had a diagnosis of AD 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). Age restrictions from the UPA phase 3 studies (12–75 years) were implemented for the real-world reference population and background rates were weighted to mimic the age and sex distribution in the combined UPA trial population. Safety cohorts were stratified by OCP use (yes vs no) among females aged 15–55 years or HRT use (yes vs no) among females aged > 55 years.

Results A total of 1178 females in the UPA phase 3 studies were evaluated (UPA 15 mg, n = 593; UPA 30 mg, n = 585). Long-term incidence rates were low for MACE and VTE (all < 0.1 n/100PY) and malignancy (exNMSC; all ≤ 0.4 n/100PY) among UPA-treated females in the OCP and non-OCP groups. There were no MACE or VTE events in patients using OCP or HRT and no malignancy (exNMSC) events in the HRT group; however, HRT results are limited by a small sample size (n = 5). While upadacitinib-treated patients using OCPs had no events of MACE or VTE, incidence rates for malignancy (excluding NMSC) from upadacitinib phase 3 studies were consistent with real-world incidence rates in patients with AD in the United States (n = 5137).

Conclusions In females with moderate-to-severe AD who received up to 6 years of UPA treatment, long-term incidence rates of MACE, VTE, and malignancy (exNMSC) were low, regardless of OCP use, and similar to those in the real-world population of patients with AD.