Brett King, MD, PhD: Value of LEVEL UP Data and Pushing New Standards in Dermatology

The value of the LEVEL UP trial goes beyond elucidating the benefit of a single agent in the management of atopic dermatitis. Even when many within a field, in this instance dermatology, suspect 1 agent may best another in a head-to-head comparison, seldom does the field ever witness this culminate in the completion of a clinical trial like LEVEL UP.

“I think the value for me of LEVEL UP is that is that we're really advancing this notion that we should be striving for clear or almost clear skin and zero or very little itch in our patients with atopic dermatitis. I've been saying this for years, but it was right in a world where there's only 1 agent, right? Which was dupilumab for the longest time,” explained Brett King, MD, PhD, associate professor of Dermatology in the Department of Dermatology at Yale University School of Medicine, in an interview with HCPLive Dermatology. “Better may have been good enough, because what else were we going to reach for, right? There was nothing else to reach for, but in a world where we have more than one choice, we shouldn't settle for better.”

Billed by AbbVie as the first head-to-head trial of upadacitinib and dupilumab in moderate-to-severe atopic dermatitis, the LEVEL UP trial was a phase 3b/4 multicenter, randomized, open-label, efficacy assessor-blinded study among patients with moderate-to-severe atopic dermatitis who had inadequate responses to systemic therapy or for whom such therapies were inadvisable. In total, 920 patients aged 12 years and older, including 803 adults and 117 adolescents, were randomized 1:1 to either upadacitinib or dupilumab.^1,2

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. Safety results indicated treatment-emergent adverse events were more common with upadacitinib (65.3% vs. 52.7%), but investigators noted the rates of severe adverse events and treatment discontinuation due to adverse events were comparable between the 2 groups.¹

To better understand the value of the trial itself as well as the results, check out our interview with King on the importance of trials like LEVEL UP in the rapidly evolving landscape of dermatology.

Relevant disclosures for King include Pfizer, Lilly USA, Eli Lilly and Company, AbbVie, Genzyme, Incite, Dermavant, Aclaris, Otsuka, Regeneron, and others.

References:

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. AbbVie News Center. New data show RINVOQ® (UPADACITINIB) demonstrated superiority versus Dupixent® (dupilumab) across primary and all secondary endpoints in an open-label head-to-head atopic dermatitis study. AbbVie News Center. April 25, 2024. Accessed June 10, 2024. https://news.abbvie.com/2024-04-25-New-Data-Show-RINVOQ-R-upadacitinib-Demonstrated-Superiority-Versus-DUPIXENT-R-dupilumab-Across-Primary-and-All-Secondary-Endpoints-in-an-Open-Label-Head-to-Head-Atopic-Dermatitis-Study.