Real world safety analysis of boxed warning adverse events for upadacitinib in atopic dermatitis using the FDA adverse event reporting system

Summary: Abstract Body: Upadacitinib, an FDA-approved oral JAK-1 selective inhibitor for moderate-severe atopic dermatitis (AD) was issued a boxed warning for serious infections, malignancies, thrombosis, and major adverse cardiovascular events (MACE) based on clinical trial findings. Real-world safety data to guide clinical decision-making remains limited. This study aims to evaluate the incidence and characteristics of adverse events (AEs) in AD patients treated with upadacitinib. AE reports from January 2004 to October 2024 were extracted from the FDA Adverse Event Reporting System (FAERS) using OpenVigil 2.1. Reports identifying upadacitinib as the primary suspect drug in AD patients were categorized using Standardized MedDRA Queries. Disproportionality analysis using reporting odds ratio (ROR) was used to evaluate AEs, with data further stratified by age and sex. 2,903 unique AE reports were identified. Higher reporting was seen in males for opportunistic infections (ROR 3.50), thrombotic events (ROR 7.34), strokes (ROR 5.45) and myocardial infarction (ROR 11.19). Opportunistic infections (ROR 4.89), sepsis (21.93), hematological malignancies (ROR 8.51), thrombotic events (ROR 13.95), strokes (ROR 18.29), and myocardial infarctions (ROR 25.91) reporting peaked in the under-30 age groups. However, solid tumors were primarily reported in the over-50 age group (ROR 6.27). These findings provide critical real-world insights into the safety profile of upadacitinib in AD. Contrasting signals between clinical trials, and our analysis of FAERS’ real-world reports highlight the need for vigilant monitoring. The increased reporting in younger age groups may partly reflect the easier attribution of AEs in patients with fewer comorbidities, emphasizing the need for providers to carefully assess individual risks. Aditya Joshi¹, Lauren Gawey¹, Khiem Tran¹, Jennifer Hsiao², Vivian Y. Shi¹ 1. Dermatology, University of Washington, Seattle, WA, United States. 2. Dermatology, University of Southern California, Los Angeles, CA, United States. Clinical Research: Epidemiology and Observational Research