Upadacitinib for moderate-to-severe atopic dermatitis: Stratified analysis from three randomized phase 3 trials by key baseline characteristics.

BACKGROUND: Atopic dermatitis (AD) is a heterogeneous inflammatory skin disease with different clinical phenotypes based on factors such as age, race, comorbidities, and clinical signs and symptoms. The effect of these factors on therapeutic responses in AD has only been scarcely studied and not for upadacitinib. Currently, there is no biomarker predicting response to upadacitinib. OBJECTIVES: Evaluate the efficacy of the oral Janus kinase inhibitor upadacitinib across patient subgroups (baseline demographics, disease characteristics and prior treatment) in patients with moderate-to-severe AD. METHODS: Data from phase 3 studies (Measure Up 1, Measure Up 2 and AD Up) were utilized for this post hoc analysis. Adults and adolescents with moderate-to-severe AD were randomized to receive once daily oral upadacitinib 15 mg, upadacitinib 30 mg or placebo; patients enrolled in the AD Up study received concomitant topical corticosteroids. Data from the Measure Up 1 and Measure Up 2 studies were integrated. RESULTS: A total of 2584 patients were randomized. A consistently greater proportion of patients achieved at least 75% improvement in the Eczema Area and Severity Index, a 0 or 1 on the validated Investigator Global Assessment for Atopic Dermatitis, and improvement in itch (including an achievement of a reduction of ≥4; and score of 0/1 in Worst Pruritus Numerical Rating Scale) with upadacitinib compared with placebo at Week 16, regardless of age, sex, race, body mass index, AD severity, body surface area involvement, history of atopic comorbidities or asthma, or previous exposure to systemic therapy or cyclosporin. CONCLUSIONS: Upadacitinib had consistently high skin clearance rates and itch efficacy across subgroups of patients with moderate-to-severe AD through Week 16. These results support upadacitinib as a suitable treatment option in a variety of patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT03569293 (Measure Up 1), NCT03607422 (Measure Up 2) and NCT03568318 (AD Up).

Higher levels of response on clinical atopic dermatitis severity measures are associated with meaningful improvements in patient-reported symptom and quality of life measures: Integrated analysis of three Upadacitinib phase 3 trials.

BACKGROUND: It is not fully understood how different degrees of improvements in atopic dermatitis (AD) clinical outcome measures translate to improvements in patient-reported outcome (PRO) measures, such as those assessing itch, symptoms, sleep, anxiety, depression, quality of life (QoL), and work productivity. OBJECTIVES: This post hoc analysis of three clinical studies assessed how more robust improvements in clinical responses are associated with improvements in PROs and QoL. METHODS: Data from three randomized, double-blind, placebo-controlled, phase 3 trials in adults and adolescents with moderate to severe atopic dermatitis (Measure Up 1, Measure Up 2, and AD Up) were included. Patients were randomly assigned (1:1:1) to upadacitinib (15 or 30 mg) or placebo once daily (alone or in combination with topical corticosteroids). The mean percentage improvement from baseline to week 16 and percentage of patients achieving responses at week 16 were summarized by the Eczema Area and Severity Index (EASI) and validated Investigator Global Assessment of Atopic Dermatitis (vIGA-AD) response level categories. RESULTS: A total of 2392 patients from the three trials were included in the analysis. Increasingly greater mean percentage improvement and proportion of patients achieving response was observed at higher clinical response levels (i.e., stepwise pattern). Mean percentage improvement and proportion of patients achieving response exceeded 69% and 70% at EASI ≥ 90 and vIGA-AD 0/1, respectively, for most PROs including Worst Pruritus Numeric Rating Scale, Patient Oriented Eczema Measure, and Dermatology Life Quality Index. CONCLUSIONS: Greater degrees of clinical responses are related to more robust improvements across multiple dimensions impacted by AD, including itch, skin pain, sleep, anxiety, depression, and QoL.