Baricitinib in Patients With Moderate-to-severe Atopic Dermatitis and Inadequate Response to Topical Corticosteroids

Results From Two Randomized Monotherapy Phase III Trials

E.L. Simpson; J.-P. Lacour; L. Spelman; R. Galimberti; L.F. Eichenfield; R. Bissonnette; B.A. King; J.P. Thyssen; J.I. Silverberg; T. Bieber; K. Kabashima; Y. Tsunemi; A. Costanzo; E. Guttman-Yassky; L.A. Beck; J.M. Janes; A.M. DeLozier; M. Gamalo; D.R. Brinker; T. Cardillo; F.P. Nunes; A.S. Paller; A. Wollenberg; K. Reich


The British Journal of Dermatology. 2020;183(2):242-255. 

In This Article

Abstract and Introduction


Background: Baricitinib, an oral selective Janus kinase 1 and 2 inhibitor, effectively reduced atopic dermatitis (AD ) severity in a phase II study with concomitant topical corticosteroids.

Objectives: To evaluate the efficacy and safety of baricitinib in patients with moderate-to-severe AD who had an inadequate response to topical therapies.

Methods: In two independent, multicentre, double-blind, phase III monotherapy trials, BREEZE -AD 1 and BREEZE -AD 2, adults with moderate-to-severe AD were randomized 2 : 1 : 1 : 1 to once-daily placebo, baricitinib 1 mg, 2 mg, or 4 mg for 16 weeks.

Results: At week 16, more patients achieved the primary end point of Validated Investigator's Global Assessment of AD (0, 1) on baricitinib 4 mg and 2 mg compared with placebo in BREEZE -AD 1 [N = 624; baricitinib 4 mg 16·8% (P < 0·001), 2 mg 11·4% (P < 0·05), 1 mg 11·8% (P < 0·05), placebo 4·8%], and BREEZE -AD 2 [N = 615; baricitinib 4 mg 13·8% (P = 0·001), 2 mg 10·6% (P < 0·05), 1 mg 8·8% (P = 0·085), placebo 4·5%]. Improvement in itch was achieved as early as week 1 for 4 mg and week 2 for 2 mg. Improvements in night-time awakenings, skin pain and quality-of-life measures were observed by week 1 for both 4 mg and 2 mg (P ≤ 0·05, all comparisons). The most common adverse events in patients treated with baricitinib were nasopharyngitis and headache. No cardiovascular events, venous thromboembolism, gastrointestinal perforation, significant haematological changes, or death were observed with any baricitinib dosage.

Conclusions: Baricitinib improved clinical signs and symptoms in patients with moderate-to-severe AD within 16 weeks of treatment and induced rapid reduction of itch. The safety profile remained consistent with prior findings from baricitinib clinical development in AD, with no new safety concerns.


Atopic dermatitis (AD) is a chronic heterogeneous inflammatory skin disease affecting up to 25% of children and 2–7% of adults globally.[1–3] AD is characterized by excessive T-cell activation influenced by genetic and environmental factors, leading to significant skin infiltration by T cells and dendritic cells.[4–7] Key cytokines in the pathogenesis of AD, such as thymic stromal lymphopoietin, interleukin (IL)-4, IL-13, IL-22 and IL-31, activate receptors that signal through the intracellular Janus kinases (JAKs) JAK1, JAK2 and tyrosine kinase 2.[4,8–10] AD treatment with baricitinib, an oral selective JAK1 and JAK2 inhibitor, may modulate many cytokines involved in AD pathogenesis, thereby mitigating disease signs and symptoms.[11]

Baricitinib is under investigation as a therapy for patients with moderate-to-severe AD who have an inadequate response to topical corticosteroids (TCS). In a 16-week phase II trial of baricitinib in moderate-to-severe AD, significantly more patients treated with baricitinib 4 mg and TCS achieved Eczema Area and Severity Index (EASI) 50 and improvements in pruritus and reduced sleep loss compared with placebo.[12] The subsequent phase III programme explores baricitinib monotherapy, in combination with TCS, and as long-term therapy. Here, we report the 16-week efficacy and safety data from the first two phase III studies of baricitinib as monotherapy in moderate-to-severe AD.