Upadacitinib Demonstrates Superior Regional, Overall Efficacy vs Dupilumab in Atopic Dermatitis: Level Up Phase 3b/4 Trial Findings
Dupilumab-treated participants with recalcitrant head and neck symptoms who were switched to upadacitinib rapidly reached EASI 75 and steadily improved, among other findings.
Findings from a new direct head-to-head clinical trial showed that upadacitinib was superior to duilumab in achieving significant skin clearance across all anatomical regions in adults and adolescents with moderate-to-severe atopic dermatitis (AD) after 16 weeks of treatment.
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The phase 3b/4 Level Up study (NCT05601882) found that a higher proportion of patients treated with upadacitinib reached Eczema Area and Severity Index (EASI) 75, 90, and 100 in the head and neck, trunk, upper limbs, and lower limbs compared to those receiving dupilumab. Further, among those who had not reached EASI 75 in the more difficult to treat head and neck regions at week 16 and were switched from dupilumab to upadacitinib, the majority achieved the 75% clearance within 4 weeks.
The data were presented in a poster at the 2025 American Academy of Dermatology Annual Meeting, held March 7-11, in Orlando, FL.
All Level Up participants had previously inadequate responses to systemic therapy or had been advised against their use, according to the study. Following random assignment to either upadacitinib (n = 458) or dupilumab (n = 462), a numerically greater proportion of participants treated with upadacitinib achieved EASI 75/90/100 as early as 2 weeks following treatment initiation in period 1 of the study and particularly in the head and neck regions, according to the poster. At week 16, rates of EASI 75 were notably higher with upadacitinib across anatomical sites: 51.8% vs 40.0% in the head and neck, 61.7% vs 46.2% in the trunk, 59.3% vs 42.0% in the upper limbs, and 68.1% vs 41.8% in the lower limbs. The investigators reported similar trends for EASI 90 and 100, indicating greater efficacy of upadacitinib in achieving near or complete skin clearance.
For participants who had not reached EASI 75 in the head and neck regions at week 16 and were switched from treatment with dupilumab to upadacitinib, improvement continued. By week 20, the majority of in this subgroup had achieved EASI 75, with continued response rates at week 32 reaching 66.7% for EASI 75, 46.5% for EASI 90, and 32.7% for EASI 100.
Skin symptoms of AD in the head and neck “may be particularly problematic for [individuals] due to their high environmental exposure and visibility,” wrote lead author Jonathan Sliverberg, MD, PhD, MPH, associate professor of dermatology, and director of clinical research and contact dermatitis at The George Washington University School of Medicine and Health Sciences in Washington, DC, and colleagues.1 The visibility of the eruption, the potential for multiple triggers, lower rates of response to therapies vs other parts of the body and greater vulnerability to the negative effects of topical steroid use, combine to create a significant individual burden on quality of life.2 The Level Up study findings suggest critical implications for treatment selection, particularly in patients who require rapid and extensive lesion resolution.
Baseline overall EASI scores were comparable between the treatment groups (27.6 for upadacitinib and 27.1 for dupilumab), ensuring a balanced comparison, the investigators wrote. Participants received either upadacitinib (15 mg starting dose, with escalation to 30 mg based on clinical response) or dupilumab, following the medication’s labeled dosing regimen. Efficacy was assessed using non-responder imputation for each body region with baseline EASI greater than zero.
