Safety and Effectiveness of Upadacitinib in Patients with Moderate-to-Severe Atopic Dermatitis Who Smoke: a 2-Year Real-Life Multicenter Study

Background: Atopic dermatitis (AD) is a chronic inflammatory skin condition that significantly impairs the quality of life. Recent advancements in systemic therapies, such as Janus kinase (JAK) inhibitors, offer very effective new treatment options. However, concerns regarding potential adverse events, including cardiovascular and thromboembolic risk, have emerged from clinical studies and call for further real-life investigations. This has highlighted the need to establish specific risk categories, such as tobacco smokers. Objective: This study aims to evaluate the safety and effectiveness of upadacitinib, a JAK1 inhibitor, in patients who smoke with moderate-to-severe AD over a 2-year treatment period, comparing outcomes with patients who do not smoke. Patients and methods: A retrospective multicenter study was conducted across 12 dermatology departments in Italy, including 375 patients treated with upadacitinib. The presence and intensity of smoking habits as well as effectiveness scores and safety data were collected. Results: Patients who smoke accounted for 36.8% of the sample. Two thromboembolic events in patients who do not smoke were recorded in the 2-year (median follow up of 52.6 weeks) observation period. The most common adverse event was acneiform eruption (12.4% of patients after 104 weeks). No significant differences related to safety emerged regarding the presence or absence of a smoking habit. Drug survival was very high with no differences between the two cohorts (83.5% after 104 weeks for patients who smoke). Conclusions: This study suggests that upadacitinib is a safe and effective treatment for moderate-to-severe AD in presence of tobacco smoke, with no significant differences in safety or effectiveness compared with patients who do not smoke.