Upadacitinib Superior in Efficacy to Dupilumab for Atopic Dermatitis in Head-to-Head Study

Topline data from the LEVEL UP trial indicate upadacitinib (Rinvoq) outperformed dupilumab (Dupixent) for the treatment of atopic dermatitis, according to an announcement from AbbVie.

Announced on April 25, 2024, data from the phase 3b/4 trial, which included patients aged ≥12 years with moderate-to-severe atopic dermatitis and either an inadequate response to or inability to use other therapies, suggest a greater proportion of patients achieved relief and resolution of symptoms with upadacitinib than with dupilumab.¹

“Too many patients are still not achieving optimal disease control in atopic dermatitis despite taking steps to manage their condition," Jonathan Silverberg, MD, PhD, MPH, director of clinical research and professor of dermatology at the George Washington University School of Medicine and Health Sciences, said in a statement. "Results from the LEVEL UP study highlight how treatment options such as upadacitinib can achieve high treatment goals in atopic dermatitis with combined measures of EASI 90 and NRS 0/1, not just itch resolution or just skin clearance."

Since receiving their initial approvals from the US Food and Drug Administration in 2017 and 2019, respectively, dupilumab and upadacitinib have become staples in the treatment algorithms for patients with a multitude of dermatologic conditions. The LEVEL UP trial was launched in 2022 to provide clinicians with greater insight into the comparative effects of these agents.

The study included design a screening period, an initial 16-week treatment period, and a subsequent 16-week period of treatment with adjustments which were protocol-defined. The study’s primary endpoint had been both a 90% or more Eczema Area and Severity Index score reduction (EASI 90) and a Worst Pruritus Numerical Rating Scale of 0 or 1 (WP-NRS 0/1) at the 16-week mark.

Upadacitinib treatment during the trial was begun at 15 mg once per day and later the dosing was escalated to 30 mg per day based upon adult and adolescent patient responses. Dupilumab was started at a dosing regimen of 600 mg, followed by 300 mg over the course of every other week (Q2W) in subjects weighing ≥60 kg, and those weighing less were given a first dose of 400 mg, followed later by a 200 mg dose Q2W.

A substantially higher percentage of subjects in the study’s conclusion were shown to have achieved both of the endpoints (19.9% versus 8.9% for upadacitinib and dupilumab, respectively, P < .0001). Among each secondary endpoint, the study’ investigators also found that upadacitinib had outperformed dupilumab.

Specifically, this had included a much higher proportion of upadacitinib-treated individuals with near complete skin clearance and little to no pruritus, with EASI 90 (40.8% versus 22.5%, P < .0001) and WP-NRS of 0/1 (30.2% versus 15.5%, P < .0001) both at the 16-week mark.

The observed safety profile for upadacitinib in LEVEL UP was consistent with previous studies in AD. No new safety concerns emerged during the study. The most common adverse events reported were nasopharyngitis for both groups. Serious adverse events occurred at the same rate (0.9%) for both medications, with one serious infection in the dupilumab group and none in the upadacitinib group. No malignancies, major adverse cardiac events, venous thromboembolic events, or treatment-related deaths were reported in either group.

References

1. ^{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. April 25, 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. Date accessed: April 25, 2024.}