Late-Breaking Data: Real-World Data from Canada Shows Upadacitinib is Effective in Patients With Moderate to Severe AD With Inadequate Response to Dupilumab

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At the 2025 Revolutionizing Atopic Dermatitis (RAD) Conference in Nashville, Tennessee, Vimal H. Prajapati, MD, presented new real-world AbbVie data from the Canadian CAN UpTIMISE study (NCT05394792) evaluating the effectiveness and safety of upadacitinib in adult patients with moderate to severe atopic dermatitis (AD) who were inadequate responders to dupilumab or who discontinued dupilumab due to safety/tolerability issues.¹ The prospective, multicenter observational study provides important insights into treatment sequencing for patients transitioning from an IL-4Rα inhibitor to a Janus kinase 1 (JAK1) selective inhibitor in routine clinical settings.

As the study authors noted, dupilumab is a widely used systemic therapy for moderate to severe AD, however, it can leave some patients with residual disease activity and/or safety/tolerability issues. With patient concerns regarding switching therapeutics or safety concerns with oral JAK inhibitors, it’s crucial for clinicians to be up to date on the latest data.

“I reassure patients who are hesitant to switch from dupilumab to upadacitinib that the clinical trial and now real-world data demonstrate that higher levels of skin clearance and itch/quality of life improvements can be achieved by switching, but that certain clinical and laboratory-related adverse events do require monitoring. I explain that most adverse effects are not serious and manageable, while serious adverse effects are infrequent,” said Prajapati, study author, clinical associate professor at the University of Calgary, and co-founder/co-director of Skin Health & Wellness Centre, Dermphi Centre, Dermphi Shop, and Dermatology Research Institute in Canada, in a statement to Dermatology Times.

Vimal H. Prajapati, MD

Study Design and Population

The study enrolled adult patients with moderate to severe AD who had been treated with dupilumab for ≥16 weeks prior to initiating upadacitinib. All treatment decisions were made prior to study enrollment and independently of the study protocol. Patients were either switched due to suboptimal disease control or safety/tolerability concerns with dupilumab. Exclusion criteria included any prior use of JAK inhibitors or recent participation in interventional trials.

Efficacy Outcomes

Clinical improvement was measured using vIGA-AD, EASI, WP-NRS, and DLQI scores. Patients received either upadacitinib 15mg or 30mg daily, with the dose determined by the treating physician based on clinical need. The primary outcome of the study was the proportion of patients achieving a vIGA-AD score of 0/1 after 4 months with upadacitinib.

• Investigator Global Assessment (vIGA-AD):
  • 65.9% of patients achieved vIGA-AD 0/1 by month 4
  • Improvement in vIGA-AD 0/1 scores was observed as early as month 1 after starting upadacitinib
• EASI Scores
  • At month 4, 90.2%, 82.9%, and 52.4% of patients had EASI scores ≤ 7, ≤ 3, and ≤ 1, respectively
  • Overall, more patients treated with upadacitinib 15mg achieved EASI score improvements compared with upadacitinib 30mg
• Pruritus Reduction (WP-NRS):
  • At month 4, 70.5% of patients achieved a WP-NRS score reduction of ≥4 who already had a baseline WP-NRS score greater than 4
  • 46.7% of patients achieved an absolute WP-NRS score of 0/1 by month 4
• Quality of Life (DLQI):
  • At month 4, 79.0% of patients achieved a DLQI score reduction of ≥4 who already had a baseline WP-NRS score greater than 4
  • 36.0% of patients achieved a DLQI score of 0/1 by month 4
• Minimal Disease Activity (EASI ≤ 3 and WP-NRS Score 0/1)
  • 43.8% of patients met minimal disease activity through the simultaneous achievement of EASI ≤ 3 and WP-NRS score 0/1 at month 4

Safety Profile

Treatment-emergent adverse events (TEAEs) were reported in 60% of patients. The majority were mild or moderate in intensity. Three patients experienced severe TEAEs; only one (constipation/inflammatory bowel disease) was possibly related to upadacitinib. Six treatment-emergent serious adverse events (TESAEs) occurred in 3 patients, which included cutaneous T-cell lymphoma, cholangitis, portal vein thrombosis, herpes simplex infection, or other infections. Notably, none of the TESAEs were deemed related to upadacitinib.

Discontinuations due to TEAEs occurred in 11 patients, most involving mild or moderate events. Eight of the discontinuations were considered related to upadacitinib. No deaths occurred during the study.

Regarding continued safety measures, Prajapati added, “All patients switching from dupilumab to upadacitinib should undergo standard baseline laboratory and radiologic investigations, which include complete blood count with differential, liver enzymes, fasting lipid profile, pregnancy test (females only), HBV/HCV/HIV serology, as well as TB testing and chest x-ray. Many dermatologists have stopped ordering serum CK levels, as the vast majority of elevated serum CK levels were asymptomatic in clinical trial and real-world data sets.”

Practice Implications

The CAN UpTIMISE study offers clinically meaningful real-world evidence that upadacitinib can achieve substantial improvements in skin clearance, itch reduction, and quality of life in adults with moderate to severe AD who had suboptimal response or safety/tolerability issues with dupilumab.

The majority of patients experienced rapid and significant relief after switching from dupilumab to upadacitinib. The safety profile was consistent with previous findings, with no new safety signals observed. These findings may inform clinical decision-making in treatment sequencing strategies for advanced AD management.

“The results of this phase 4 real-world study show that if patients are not achieving adequate responses to or having safety/tolerability issues with dupilumab, switching to upadacitinib can provide incremental benefits for efficacy, without any new safety signals. Our findings support the new paradigm shift that dermatologists should strive for higher levels of skin clearance and itch/quality of life improvements (eg, optimal minimal disease activity targets), as this correlates with better patient outcomes,” Prajapati concluded.

Reference

1. Hong H, Lynde C, Jain V, et al. Effectiveness and safety of upadacitinib in Canadian adult patients with atopic dermatitis who were inadequate responders or intolerant to dupilumab: results from the CAN UpTIMISE phase 4 multicentre study. Presented at: 2025 Revolutionizing Atopic Dermatitis Conference; June 6-7; 2025; Nashville, TN