New topline results evaluating the efficacy and safety of upadacitinib for adults and adolescents with moderate-to-severe atopic dermatitis (AD) who had an inadequate response to systemic therapy or when use of those therapies was inadvisable suggested that treatment with the drug was effective.

The study, LEVEL UP, was a Phase 3b/4, multi-center, randomized, open-label, efficacy assessor-blinded study comprising a 35-day screening period, a 16-week treatment Period 1, and a 16-week treatment Period 2. During Period 1, participants were randomly assigned in one of two groups to receive upadacitinib (RINVOQ®) 15 mg QD or dupilumab as per its label. In Period 2, participants received upadacitinib as per protocol-defined criteria. The primary endpoint 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. Key ranked secondary endpoints included the 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 >1. The mean body surface area (BSA) among patients enrolled in the study was 38%, and 42% of patients had severe disease (vIGA-AD = 4) at baseline

"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," said Roopal Thakkar, MD, AbbVie’s senior vice president, chief medical officer, global therapeutics, in an AbbVie press release. "Results from this study show that patients with moderate-to-severe atopic dermatitis can strive for both little to no itch and clearer skin."

According to the results, upadacitinib showed superior efficacy in the primary endpoint, with a significantly higher proportion of patients simultaneously achieved both 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 [(19.9% vs 8.9%, p<0.0001)].¹ Upadacitinib also showed superiority for all ranked secondary endpoints, including the rapid onset of achieving near complete skin clearance and no to little itch. For the first two ranked secondary endpoints, the study showed that a significantly higher proportion of patients treated with upadacitinib:

• Achieved EASI 90 at Week 16 [(40.8% vs 22.5%, p<0.0001)].¹
• Achieved a WP-NRS of 0/1 at Week 16 [(30.2% vs 15.5%, p<0.0001)] ¹;his endpoint was evaluated among patients with a baseline WP-NRS >1.

AbbVie plans to present results from the LEVEL UP study at a future medical congress.

According to the AbbVie news release, LEVEL UP study is the first head-to-head trial in atopic dermatitis assessing upadacitinib at a starting dose of 15 mg daily versus dupilumab at its labeled dose. Upadacitinib was initiated in adults and adolescents (≥12 years of age, weighing at least 40 kg) at 15 mg once daily (QD) and dose-escalated to 30 mg QD based on clinical response. Dupilumab was initiated at 600 mg, followed by 300 mg every other week (Q2W) in adults and adolescents weighing ≥60 kg; adolescents weighing less than 60 kg received an initial dose of 400 mg, followed by 200 mg Q2W.¹

"Too many patients are still not achieving optimal disease control in atopic dermatitis despite taking steps to manage their condition," 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, in a news release. "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."

No new safety signals were identified during the study period.¹ In Period 1, the most common adverse events (AE) reported were nasopharyngitis for both the upadacitinib and dupilumab group.¹ The rate of serious AEs (0.9%) was the same for both upadacitinib and dupilumab. There was one serious infection reported in the dupilumab group and none in the upadacitinib group.¹ No malignancies, adjudicated major adverse cardiac events, adjudicated venous thromboembolic events (VTEs) or treatment-emergent deaths were reported in either treatment group.¹

References

1. AbbVie. Data on File ABVRRTI78473.
2. RINVOQ [Package Insert]. North Chicago, IL: AbbVie Inc.; 2023.