AbbVie recently announced new topline data from its phase 3b/4 study, LEVEL-UP (NCT05601882), an open-label, efficacy assessor-blinded head-to-head study evaluating the safety and efficacy of upadacitinib 15mg once daily (Rinvoq) compared to dupilumab (Dupixent; Sanofi and Regeneron) in adolescent and adult patients with moderate to severe AD who had inadequate responses to systemic therapies or who should not use systemic therapies.

Upadacitinib demonstrated superior efficacy compared to dupilumab in the primary end point of 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. Overall, 19.9% of patients treated with upadacitinib achieved the primary end point and 8.9% of patients treated with dupilumab achieved the primary end point.

"Too many patients are still not achieving optimal disease control in atopic dermatitis despite taking steps to manage their condition. 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,” said Jonathan Silverberg, MD, PhD, MPH, professor of dermatology and director of clinical research at the George Washington University School of Medicine and Health Sciences and lead study investigator, in the news release.

Additionally, upadacitinib demonstrated superiority compared to dupilumab in all ranked secondary end points, including the rapid onset of achieving near complete skin clearance and little to no itch. Other secondary end points included 40.8% of patients treated with upadacitinib achieved EASI-90 at week 16 compared to 22.5% of patients treated with dupilumab, and 30.2% of patients treated with upadacitinib achieved a WP-NRS of 0 or 1 at week 16 compared to 15.5% of patients treated with dupilumab.

"Even while receiving conventional treatments, many patients with atopic dermatitis still continue to live with significant itch and inflammatory skin symptoms that can profoundly impact their everyday lives. Results from this study show that patients with moderate-to-severe atopic dermatitis can strive for both little to no itch and clearer skin,” said Roopal Thakkar, MD, senior vice president and chief medical officer of global therapeutics at AbbVie, in the news release.

LEVEL-UP is the first head-to-head trial in atopic dermatitis evaluating upadacitinib beginning at 15 mg daily compared to dupilumab and its labeled dose. Upadacitinib was first dosed in adult and adolescent patients aged 12 years and older and weighing at least 40 kg at 15 mg once a day, and then increased to 30 mg once a day based on their clinical response. Dupilumab was first dosed at 600 mg, followed by 300 mg every other week in adult and adolescent patients weighing at least 60 kg. Any adolescent patients who weighed less than 60 kg received a first dose of 400 mg, followed by 200 mg every other week.

Upadacitinib’s safety profile was consistent with previous atopic dermatitis studies and no new safety signals were identified in LEVEL-UP. During the first 16 weeks, the most common adverse events were nasopharyngitis for both the upadacitinib and dupilumab patient groups. No malignancies, adjudicated major adverse cardiac events, adjudicated venous thromboembolic events, or treatment-emergent deaths were reported in either patient group.

According to the announcement, AbbVie plans to present the results from LEVEL-UP at a future medical congress.

Reference

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. News release. AbbVie. April 25, 2024. Accessed 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