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

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. 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. 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. 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. NCT05394792. Atopic dermatitis, also called eczema, is a long-lasting skin condition that causes itching, redness, scaling, and pain. It affects millions of people worldwide and can significantly impact daily life. This study was conducted in Canada at 25 community-based dermatology and allergy clinics. We wanted to understand how well upadacitinib works and how safe it is for adults with moderate-to-severe atopic dermatitis who did not respond well to dupilumab or stopped dupilumab because of side effects. The study followed 108 adults who switched from dupilumab to upadacitinib. Doctors prescribed upadacitinib according to the approved Canadian label, and patients were monitored for about 4 months. We measured skin clearance, itch relief, and quality of life improvements using standard clinical and patient questionnaires. By month 4, two-thirds of patients (66%) had clear or almost clear skin. Improvements in visible skin disease, itch, and quality of life were seen as early as month 1. About 44% of patients reached “minimal disease activity,” meaning clear or almost clear skin and no or almost no itch. Side effects were generally mild or moderate, and no new safety concerns were found. Upadacitinib provided meaningful improvements for patients with atopic dermatitis who did not respond well to or could not tolerate dupilumab. These results suggest upadacitinib is an effective and well-tolerated treatment option for managing patients with moderate-to-severe atopic dermatitis in real-world practice.