Upadacitinib Shows Greater Skin Clearance Than Dupilumab in Atopic Dermatitis

New findings presented at the 2025 American Academy of Dermatology (AAD) Annual Meeting demonstrate that at the 16-week mark, a higher proportion of those treated with upadacitinib, attained skin clearance in atopic dermatitis across all regions of the body compared to dupilumab.1

These findings resulted from the phase 3b/4 Level Up trial (NCT05601882), during which investigators, including Kilian Eyerich, MD, PhD, a chair and professor at the department of dermatology and venerology for the University of Freiburg, assessed adolescents and adults with moderate-to-severe atopic dermatitis.

“Here we evaluate skin clearance by body region in the Level Up head to head trial for patients with moderate to severe [atopic dermatitis],” Eyerich and the other investigators wrote.1

The inflammatory skin condition is known to impact a variety of bodily regions. Eyerich et al. looked at the impact of a selective oral Janus kinase (JAK)-inhibitor, upadacitinib, and a monoclonal antibody that inhibits interleukin (IL)-4 and IL-13 signaling, dupilumab. Both medications are approved by the US Food and Drug Administration (FDA) for patients with atopic dermatitis.2,3

In Level Up, the investigative team looked at adolescents and adults with atopic dermatitis and reported inadequate responses to systemic drugs or were instructed that such therapies were inadvisable.

The phase 3b/4 study had an open-label, global, randomized, efficacy assessor-blinded, multi-center, head-to-head design. Investigators evaluated participants treated with upadacitinib and compared the results with those treated with dupilumab following a 16-week course.1

The team looked at a variety of endpoints, placing specific focus on improvements in participants’ Eczema Area and Severity Index (EASI) scores of ≥75/90/100% (EASI 75/90/100). These improvements in symptoms were evaluated from baseline, with investigators looking at 4 specific regions of anatomy: heads and necks, upper trunk, limbs, and lower limbs.

In 1 arm of the study, those involved in Level Up were randomized to upadacitinib 15mg as an initial dose, with the potential for treatment escalation to 30 mg doses based on clinical responses. In the other arm, participants were treated with dupilumab, as labeled, for the first 16 weeks of therapy. Investigators evaluated EASI 75/90/100 responses for each body area for patients with a baseline body region EASI >0 through non-responder imputation.

A total of 458 individuals were randomized to the upadacitinib cohort and 462 to the dupilumab cohort. By the 16-week mark, Eyerich and colleagues highlighted several notable findings among the Level Up participants.

They pointed to a higher proportion of those in the upadacitinib group attaining an EASI 75 score in their head and neck regions (51.8%) compared to only 40.0% in the dupilumab group. This was also observed in the trunk region (61.7% versus 46.2%, respectively), the upper limbs (59.3% versus 42.0%, respectively), and the lower limbs (68.1% versus 41.8%, respectively).1

In their observation of shifts in EASI 90 and 100 score attainment, the investigative team noted comparable trends. Overall, the team highlighted that, starting at the 2-week mark, all bodily areas saw a numerically higher proportion of those in the upadacitinib arm achieving EASI 75/90/100 versus dupilumab.

“Numerically higher EASI 75/90/100 response rater were maintained through week 16 across all body regions compared with dupilumab,” Eyerich and colleagues wrote.1

For additional information on data presented at AAD 2025, view our latest conference coverage here.

References

1. Eyerich K, Torres T, Silverberg J, et al. Higher Levels of Skin Clearance Across Body Regions with Upadacitinib versus Dupilumab in Patients with Moderate-to-Severe Atopic Dermatitis. Presented at the 2025 American Academy of Dermatology (ADA) Annual Meeting. Orlando, FL. March 07-11, 2025.

2. Butera A. FDA Approves Upadacitinib for Patients 12 Years and Older with Moderate to Severe Atopic Dermatitis. HCPLive. January 14, 2022. https://www.hcplive.com/view/fda-upadacitinib-children-atopic-dermatitis. Date accessed: March 13, 2025.

3. Regeneron and Sanofi Announce FDA Approval of DUPIXENT® (dupilumab), the First Targeted Biologic Therapy for Adults with Moderate-to-Severe Atopic Dermatitis. Regeneron. March 28, 2017. https://investor.regeneron.com/news-releases/news-release-details/regeneron-and-sanofi-announce-fda-approval-dupixentr-dupilumab/#:~:text=March%2028%2C%202017%20at%2011,those%20therapies%20are%20not%20advisable. Date accessed: March 13, 2025.