Background: Atopic dermatitis is a chronic inflammatory skin disease characterized by pruritic skin lesions.
Objective: We sought to evaluate the safety and efficacy of multiple doses of the selective Janus kinase 1 inhibitor upadacitinib in patients with moderate to severe atopic dermatitis.
Methods: In the 16-week, double-blind, placebo-controlled, parallel-group, dose-ranging portion of this 88-week trial in 8 countries (ClinicalTrials.gov, NCT02925117; ongoing, not recruiting), adults with moderate to severe disease and inadequate control by topical treatment were randomized 1:1:1:1, using an interactive response system and stratified geographically, to once-daily upadacitinib oral monotherapy 7.5, 15, or 30 mg or placebo. The primary end point was percentage improvement in Eczema Area and Severity Index from baseline at week 16. Efficacy was analyzed by intention-to-treat in all randomized patients. Safety was analyzed in all randomized patients who received study medication, based on actual treatment.
Results: Patients (N = 167) enrolled from November 21, 2016, to April 20, 2017. All were randomized and analyzed for efficacy (each upadacitinib group, n = 42; placebo, n = 41); 166 were analyzed for safety (each upadacitinib group, n = 42; placebo, n = 40). The mean (SE) primary efficacy end point was 39% (6.2%), 62% (6.1%), and 74% (6.1%) for the upadacitinib 7.5-, 15-, and 30-mg groups, respectively, versus 23% (6.4%) for placebo (P = .03, <.001, and <.001). Serious adverse events occurred in 4.8% (2 of 42), 2.4% (1 of 42), and 0% (0 of 42) of upadacitinib groups (vs 2.5% [1 of 40] for placebo).
Conclusions: A dose-response relationship was observed for upadacitinib efficacy; the 30-mg once-daily dose showed the greatest clinical benefit. Dose-limiting toxicity was not observed.
Keywords: Atopic dermatitis; Janus kinase; eczema; efficacy; placebo-controlled; randomized clinical trial; safety; upadacitinib.
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.