Real-World Evidence of Upadacitinib in Atopic Dermatitis after Inadequate Response or Intolerance to Dupilumab: The CAN UpTIMISE Study.

INTRODUCTION: Upadacitinib and dupilumab are both approved treatments for moderate-to-severe atopic dermatitis (AD). Some dupilumab-treated patients may experience an inadequate response and/or safety/tolerability issues. Real-world data on the effectiveness of upadacitinib in this population remain limited. The objective was to evaluate the effectiveness and safety of upadacitinib in adults diagnosed with moderate-to-severe AD who were inadequate responders to dupilumab or discontinued dupilumab for safety/tolerability reasons. METHODS: CAN UpTIMISE was a Canadian prospective, observational study in adults treated with dupilumab for moderate-to-severe AD with a decision to switch to upadacitinib (15/30 mg), per local label. Effectiveness was assessed over 4 months using the validated Investigator Global Assessment for AD (vIGA-AD), facial IGA, Eczema Area and Severity Index (EASI), Worst Pruritus Numerical Rating Scale (WP-NRS), Dermatology Life Quality Index (DLQI), and Patient Oriented Eczema Measurement (POEM). Results are presented using descriptive statistics. RESULTS: Among 108 patients (94.4% with vIGA-AD ≥ 2), 83.3% discontinued dupilumab due to inadequate effectiveness and 16.7% discontinued due to safety/tolerability reasons. At month 4, 65.9% (95% CI 55.1-75.2) achieved vIGA-AD 0/1 by observed case analysis (primary outcome), with improvements evident as early as month 1. At month 4 after upadacitinib initiation, 90.2%, 82.9%, and 52.4% of patients achieved EASI ≤ 7, ≤ 3, and ≤ 1, respectively; 70.5% with baseline WP-NRS > 4 had ≥ 4-point reduction and 46.7% reported WP-NRS 0/1. DLQI and POEM scores improved similarly, with 36.0% and 34.3%, respectively, achieving scores indicating no impact or clear/almost clear disease. Minimal disease activity (EASI ≤3 and WP-NRS 0/1) was reached by 43.8% of patients. Upadacitinib was generally well tolerated and no new safety signals were identified. CONCLUSIONS: Upadacitinib provided rapid, clinically meaningful, and generally sustained improvements in disease activity, itch, and quality of life, supporting its role as an effective and well-tolerated treatment for patients with inadequate response or intolerance to dupilumab in real-world practice. Graphical abstract available for this article. TRIAL REGISTRATION: NCT05394792.