Jonathan Silverberg, MD, PhD, MPH: LEVEL UP Aids in Clinical Decision-Making for Atopic Dermatitis

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Jonathan Silverberg, MD, PhD, MPH, discusses how the results of the LEVEL UP trial impact treatment decisions for patients with moderate-to-severe atopic dermatitis.

Data from the LEVEL UP trial indicate upadacitinib outperformed dupilumab for reaching EASI 90 and improvements in itch among patients with moderate-to-severe atopic dermatitis.

Billed as the first head-to-head trial of upadacitinib and dupilumab in moderate-to-severe atopic dermatitis, the LEVEL UP trial was launched in 2022. A phase 3b/4 multicenter, randomized, open-label, efficacy assessor-blinded study, the trial enrolled patients with moderate-to-severe atopic dermatitis who had inadequate responses to systemic therapy or for whom such therapies were inadvisable.1,2

In total, the study enrolled 920 patients aged 12 years and older, including 803 adults and 117 adolescents. These patients were randomized 1:1 to either upadacitinib or dupilumab, with 458 patients randomized to upadacitinib and 462 to dupilumab.1

The primary endpoint was the simultaneous achievement of a 90% or greater reduction in the Eczema Area and Severity Index (EASI 90) and a Worst Pruritus Numerical Rating Scale (WP-NRS) score of 0 or 1 at week 16. Key secondary endpoints included achievement of EASI 90 and WP-NRS of 0/1 at week 16 among patients with a baseline WP-NRS greater than 1.1

Results demonstrated a significantly higher proportion of patients achieving the primary endpoint with upadacitinib compared to dupilumab (19.9% vs. 8.9%; P <.0001). Similarly, upadacitinib outperformed dupilumab in achieving both EASI 90 (40.8% vs. 22.5%; P <.0001) and WP-NRS of 0/1 (30.2% vs. 15.5%; P <.0001) at week 16.1

Safety analysis revealed that treatment-emergent adverse events were more common with upadacitinib (65.3% vs. 52.7%). However, the rates of severe adverse events and treatment discontinuation due to adverse events were comparable between the 2 groups. A single serious infection occurred with dupilumab, while 5 opportunistic infections were reported with upadacitinib.1

For more on the trial and the impact of its findings, check out our interview with principal investigator Jonathan Silverberg, MD, PhD, MPH, professor of dermatology and director of clinical research at the George Washington University School of Medicine and Health Science.

Relevant disclosures of interest for Silverberg include AbbVie, lamar, Aldena, Amgen, AObiome, Arcutis, Arena, Asana, Aslan, BioMX, Biosion, Bodewell, Boehringer-Ingelheim, Bristol-Myers Squibb, and others.


  1. Silverberg JI, Bunick C, Hong C, et al. Efficacy and Safety of Upadacitinib vs Dupilumab in Adults and Adolescents with Moderate-to-Severe Atopic Dermatitis: Results of an Open-label, Efficacy Assessor-Blinded Head-to-Head Phase 3b/4 Study (Level Up). Abstract presented at Revolutionizing Atopic Dermatitis 2024. Chicago, Il. June 08-10, 2024.
  2. A Study to Evaluate Adverse Events and Change in Disease Activity Comparing Oral Upadacitinib to Subcutaneous Dupilumab in Adolescent and Adult Participants With Moderate to Severe Atopic Dermatitis (Level Up). Accessed June 10, 2024.