AbbVie Announces Publication of Pivotal Global Phase 3 Results for JAK Inhibitor Upadacitinib in Moderate-to-Severe Atopic Dermatitis

Article Source: Yiyao Guanlan

Recently, AbbVie announced that *The Lancet* has published the primary analysis results of its pivotal global Phase 3 clinical trials—Measure Up 1, Measure Up 2, and AD Up—evaluating the JAK inhibitor upadacitinib for moderate-to-severe atopic dermatitis. According to the press release, upadacitinib met all primary and secondary endpoints across all three studies, with the results published in two separate articles.

Upadacitinib (Rinvoq, upadacitinib), discovered and developed by AbbVie scientists, is a once-daily, oral, selective and reversible JAK1 inhibitor. JAK1 plays a critical role in the pathophysiology of immune-mediated diseases. In August 2019, upadacitinib received U.S. FDA approval for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to or intolerance of methotrexate. For moderate-to-severe atopic dermatitis, upadacitinib was granted Breakthrough Therapy designation by the FDA and was included in the Priority Review program by China's National Medical Products Administration (NMPA).

According to the press release, the study published in *The Lancet* primarily evaluated the use of upadacitinib in adult and adolescent patients with moderate-to-severe atopic dermatitis who are candidates for systemic therapy. Specifically, the Measure Up 1 and Measure Up 2 trials assessed the efficacy and safety of upadacitinib (15 mg or 30 mg, once daily) monotherapy versus placebo over 16 weeks. The AD Up trial evaluated the efficacy and safety of upadacitinib at either dose in combination with topical corticosteroids (TCS) compared with placebo plus TCS over a 16-week treatment period.

The results demonstrated that across all three studies, compared with placebo, upadacitinib significantly improved lesion clearance and reduced itch in adult and adolescent patients with moderate-to-severe atopic dermatitis. Treatment with upadacitinib met the composite primary endpoint, including ≥75% improvement from baseline in the Eczema Area and Severity Index at Week 16 (EASI 75), and a validated Investigator’s Global Assessment for Atopic Dermatitis (vIGA-AD) score of 0 or 1 (clear or almost clear). Additionally, among patients receiving either dosing regimen of upadacitinib, a substantial proportion achieved clinically meaningful itch reduction, defined as a decrease from baseline of ≥4 points on the peak itch Numeric Rating Scale (NRS) score.

In the aforementioned three pivotal Phase 3 studies in atopic dermatitis, the safety profile of upadacitinib was consistent. Compared with the safety profile observed in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis treated with upadacitinib, no new safety risks associated with upadacitinib were observed in these three studies.

Dr. Michael Severino, Vice Chairman and President of AbbVie, stated: “Despite advances in treatment, patients with moderate-to-severe atopic dermatitis continue to suffer from itching and skin symptoms that significantly impact their daily lives. The submission of these data marks an important step in our commitment to bringing more treatment options to people battling this often underestimated and debilitating disease.”

Previously, upadacitinib also demonstrated positive results in the Heads Up study, providing robust head-to-head clinical data in the field of atopic dermatitis. The study evaluated the efficacy and safety of upadacitinib versus the comparator (dupilumab) in adult patients with moderate-to-severe atopic dermatitis who were eligible for systemic therapy. In the study, patients were randomized to receive upadacitinib (30 mg once daily) or the comparator (300 mg every other week) as monotherapy for 24 weeks.

In December 2020, AbbVie announced the primary results of the Heads Up study: in adult patients with moderate-to-severe atopic dermatitis, upadacitinib met the primary endpoint of superiority compared to the comparator. At Week 16, 71% of patients treated with upadacitinib achieved EASI 75, compared with 61% of patients receiving the comparator (p = 0.006). Upadacitinib also demonstrated superiority over the comparator across all hierarchically tested key secondary endpoints, including additional measures of skin clearance and itch reduction.

Atopic dermatitis is a chronic, relapsing, inflammatory skin disease characterized by intermittent pruritus and scratching, leading to skin fissuring, desquamation, and exudation. It is estimated that 10% of adults and 25% of adolescents are affected by this disease. Twenty to 46% of adult patients with atopic dermatitis have moderate-to-severe disease, imposing a substantial physical, psychological, and economic burden on patients.

Note: The original text has been abridged.

References:

[1]Guttman-Yassky E., et al. Once-daily upadacitinib versus placebo in adolescents and adults with moderate-to-severe atopic dermatitis (Measure Up 1 and Measure Up 2): results from two replicate, double-blind, randomized controlled phase 3 studies. Lancet. doi:10.1016/s0140-6736(21)00588-2.

[2]Reich K., et al. Safety and efficacy of upadacitinib in combination with topical corticosteroids in adolescents and adults with moderate-to-severe atopic dermatitis(AD Up): results from a randomized, double-blind, placebo-controlled phase 3 trial. Lancet. doi:10.1016/s0140-6736(21)00589-4.

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