Baricitinib in patients with moderate-to-severe atopic dermatitis and inadequate response to topical corticosteroids: results from two randomized monotherapy phaseIIItrials

Background Baricitinib, an oral selective Janus kinase 1 and 2 inhibitor, effectively reduced atopic dermatitis (AD) severity in a phaseIIstudy with concomitant topical corticosteroids. Objectives To evaluate the efficacy and safety of baricitinib in patients with moderate-to-severeADwho had an inadequate response to topical therapies. Methods In two independent, multicentre, double-blind, phaseIIImonotherapy trials,BREEZE-AD1 andBREEZE-AD2, adults with moderate-to-severeADwere 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 ofAD(0, 1) on baricitinib 4 mg and 2 mg compared with placebo inBREEZE-AD1 [N= 624; baricitinib 4 mg 16 center dot 8% (P< 0 center dot 001), 2 mg 11 center dot 4% (P< 0 center dot 05), 1 mg 11 center dot 8% (P< 0 center dot 05), placebo 4 center dot 8%], andBREEZE-AD2 [N= 615; baricitinib 4 mg 13 center dot 8% (P= 0 center dot 001), 2 mg 10 center dot 6% (P< 0 center dot 05), 1 mg 8 center dot 8% (P= 0 center dot 085), placebo 4 center dot 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 center dot 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-severeADwithin 16 weeks of treatment and induced rapid reduction of itch. The safety profile remained consistent with prior findings from baricitinib clinical development inAD, with no new safety concerns. What is already known about this topic? Atopic dermatitis (AD) is a chronic heterogeneous inflammatory skin disease with few approved therapies for patients with moderate-to-severe disease. What does this study add? These two phase III trials show that baricitinib, an oral inhibitor of Janus kinase 1 and 2, significantly improved clinical signs and symptoms of AD compared with placebo within the first 16 weeks of treatment. Baricitinib may represent a first-in-class oral treatment option for adult patients with moderate-to-severe AD.