Upadacitinib in adults with moderate to severe atopic dermatitis: 16-week results from a randomized, placebo-controlled trial

Abstract

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 oncedaily 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 5 167) enrolled from November 21, 2016, to April 20, 2017. All were randomized and analyzed for efficacy (each upadacitinib group, n 5 42; placebo, n 5 41); 166 were analyzed for safety (each upadacitinib group, n 5 42; placebo, n 5 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 5 .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.

Quantifying patient preferences for systemic atopic dermatitis treatments using a discrete-choice experiment

“…abrocitinib, baricitinib, and upadacitinib) and injectable anti-IL-13 antibodies (i.e. tralokinumab and lebrikizumab) that have shown promise in early-phase clinical studies [17][18][19][20][21][22].…”

New and Emerging Systemic Treatments for Atopic Dermatitis

“…Of note, this study is the first to evaluate selective JAK1 inhibition in AD patients without concomitant corticosteroid use. Only two serious TEAEs were reported in the treatment group, including jaw pericoronitis in a subject with a history of dental infections and worsening AD in another subject [44]. There were no dose-dependent adverse events.…”

“…Several phase III clinical trials evaluating upadacitinib in subjects with AD are ongoing ( Table 2). In a phase IIb RCT in adults with AD, by week 16, a higher percentage of subjects receiving upadacitinib (7.5, 15, or 30 mg) achieved an EASI-75 than the group receiving placebo (p ≤ 0.001, p ≤ 0.001, p ≤ 0.05, respectively) [44]. Additionally, by week 16, a higher proportion of subjects receiving upadacitinib (7.5, 15, or 30 mg) achieved an IGA of 1 or 0 than the group receiving placebo (p ≤ 0.001, p ≤ 0.001, p ≤ 0.05, respectively).…”

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“…More recently, results have been published from a phase IIb trial of upadacitinib in atopic dermatitis [38]. A total of 167 patients with moderate-to-severe atopic dermatitis were randomized to placebo or upadacitinib 7.5 mg, 15 mg, or 30 mg. All doses of upadacitinib met the primary endpoint of percentage improvement in Eczema Area and Severity Index at Week 16, with no dose-limiting toxicity observed [38]. Phase III trials of upadacitinib in atopic dermatitis are ongoing (NCT03607422, NCT03738397, NCT03568318, and NCT03569293).…”