LEVEL UP: Upadacitinib Bests Dupilumab for Moderate-to-Severe Atopic Dermatitis

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LEVEL UP data presented at RAD 2024 provide additional insight into the phase 3b/4 trial comparing upadacitinib and dupilumab in atopic dermatitis beyond the primary endpoint.

Jonathan Silverberg, MD, PhD, MPH | Credit: George Washington University

Jonathan Silverberg, MD, PhD, MPH
Credit: George Washington University

Full data from the landmark LEVEL UP trial presented at the Revolutionizing Atopic Dermatitis (RAD) 2024 Annual Meeting provide the deepest insight yet into the comparative safety and efficacy of upadacitinib relative to dupilumab in moderate-to-severe atopic dermatitis, with upadacitinib besting dupilumab for the trial’s primary and key secondary endpoints.

The presentation, which comes less than 2 months after AbbVie announced topline data from the trial, provide additional insight into the comparative effectiveness of upadacitinib relative to dupilumab, including key safety considerations, among adults and adolescents with moderate-to-severe atopic dermatitis who had an inadequate response to systemic therapy or when use of those therapies was inadvisable.1,2

“So, as we're approaching that conversation, I'm a big believer in shared decision making and that we should offer options to patients and see what really resonates based on their preferences and goals,” said 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, in an interview with HCPLive. “These data really provide important context in terms of superior efficacy for upadacitinib over dupilumab and potentially other biologics by extension."

Launched in 2022, LEVEL UP is a phase 3b/4, multicenter, randomized, open-label, efficacy assessor-blinded study designed to assess the efficacy and safety of upadacitinib and dupilumab among patients with moderate-to-severe atopic dermatitis who had inadequate response to systemic therapy or when use of those therapies was inadvisable. Approved in moderate-to-severe atopic dermatitis in 2022 and 2017, respectively, LEVEL UP is billed by AbbVie as the first head-to-head trial of upadacitinib and dupilumab in this patient population.1,3,4,5

The trial included 920 patients aged 12 years or older, including 803 adults and 117 adolescents, who were randomized in a 1:1 ratio to either upadacitinib or dupilumab. In total, 458 patients were randomized to upadacitinib and 462 were randomized to dupilumab.1

The trial included a 35-day screening period and 2, 16-week treatment periods. In treatment period 1, patients were randomized to upadacitinib 15 mg once daily or dupilumab according to label information. In period 2, patients received upadacitinib as per protocol-defined criteria. Of note, period 2 consisted of patients who did not achieve the primary endpoint during the first 16-week treatment period.1

The trial’s primary outcome of interest was the simultaneous achievement of a 90% or greater reduction in Eczema Area and Severity Index (EASI 90) and a Worst Pruritus Numerical Rating Scale of 0 or 1 (WP-NRS 0/1) at Week 16. The trial also included multiple key secondary endpoints, such as achievement of EASI 90 at Week 16, and the achievement of a WP-NRS of 0/1 at week 16 among those with a Baseline WP-NRS greater than 1.1

Results of the study indicated use of upadacitinib was associated with a significantly greater proportion of patients achieving the trial’s primary endpoint than use of dupilumab (19.9% vs 8.9%; P < .0001). Further analysis of individual components of the primary endpoint demonstrated a similar trend for both achievement of EASI 90 (40.8% vs 22.5%; P <.0001) and achievement of a WP-NRS of 0/1 (30.2% vs 15.5%; P <.0001) at week 16.1

Safety analysis suggested treatment-emergent adverse event occurred at a greater frequency among those receiving upadacitinib than dupilumab (65.3% vs 52.7%). However, the incidence of severe adverse events and adverse events leading to discontinuation of study treatment were similar between both arms.1

When assessing risk of infection, results indicated a single serious infection was reported with use of dupilumab while none were reported with upadacitinib. However, investigators pointed out 5 opportunistic infections occurred with upadacitinib, all of which were eczema herpeticum, and none occurred with dupilumab.1

“We certainly look for, or hope, for treatments that can get us to higher rates of patients achieving a clinical response across the treated patient population," Silverberg added. "Well, you have upadacitnib [that] in particular, is able to really fill a lot of those unmet needs and a lot of our sense of its ability to fill the unmet needs was already sort of generated from previous studies and the LEVEL UP study really just adds to that.”

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.
  3. Clinicaltrials.gov. 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). Clinicaltrials.gov. Accessed June 10, 2024. https://clinicaltrials.gov/study/NCT05601882.
  4. AbbVie News Center. U.S. FDA approves RINVOQ® (upadacitinib) to treat adults and children 12 years and older with refractory, moderate to severe atopic dermatitis. AbbVie News Center. January 14, 2022. Accessed June 10, 2024. https://news.abbvie.com/2022-01-14-U-S-FDA-Approves-RINVOQ-R-upadacitinib-to-Treat-Adults-and-Children-12-Years-and-Older-with-Refractory,-Moderate-to-Severe-Atopic-Dermatitis.
  5. Office of the Commissioner. FDA approves New Eczema Drug Dupixent. U.S. Food and Drug Administration. March 28, 2017. Accessed June 10, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-new-eczema-drug-dupixent.

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