26670 The contribution of itch and skin severity improvements to the Dermatology Life Quality Index in patients with atopic dermatitis in a baricitinib phase 3 study, BREEZE-AD5

BREEZE-AD5 (NCT03435081), a placebo (PBO)-controlled, phase 3, monotherapy trial, demonstrated the safety and efficacy of baricitinib (BARI), an oral selective Janus kinase 1/2 (JAK1/JAK2) inhibitor, for the treatment of moderate-to-severe atopic dermatitis in US and Canadian adults with previously inadequate or intolerable responses to topical therapy. This post hoc, multiple mediator analysis of BREEZE-AD5 analyzed whether improvement in itch (measured by the change from baseline in a numeric rating scale) or in skin severity (measured by the change from baseline in Eczema Area and Severity Index [EASI] or in Body Surface Area [BSA]) mediated the treatment effect over PBO on changes in the Dermatology Life Quality Index (DLQI). Patients (N = 440) were randomized 1:1:1 to once daily PBO, BARI-1 mg or 2-mg; BARI 2-mg is the focus of this analysis. Missing data were imputed using modified last observation carried forward. At Week 16, the following least-squares mean changes were observed for PBO and BARI 2-mg, respectively: −4.67 and −12.03 in EASI (P < .001); −5.95 and −15.84 in BSA (P < .001); −0.78 and −2.39 in itch (P < .001), and −1.97 and −6.52 in DLQI (P < .001). Changes in itch and EASI, respectively, accounted for 52% and 26% improvement in DLQI, and for changes in itch and BSA, these values were 56% and 17%. Similar results were observed at Week 4. BARI 2-mg demonstrated improvement in DLQI and approximately half of the changes in DLQI at Weeks 4 and 16 were mediated by improvements in itch.