Ruxolitinib Cream Suppresses Th2 Inflammation in Adult Patients With Atopic Dermatitis

Abstract

Ruxolitinib cream, a selective inhibitor of Janus kinases (JAK)-1 and JAK2, potently inhibits proinflammatory cytokine signaling involved in atopic dermatitis (AD) pathogenesis. In a phase 2 trial, 1.5% ruxolitinib cream twice daily (BID) demonstrated efficacy at least comparable to triamcinolone. Rapid decreases in itching were observed. The effects of ruxolitinib cream on Th2 biomarkers and the relationship with clinical measures in this trial are reported below. Sera were collected from 111 patients treated with ruxolitinib cream 0.15% once daily (QD; n=17), 0.5% QD (n=20), 1.5% QD (n=15), 1.5% BID (n=18), triamcinolone BID (n=19), and vehicle BID (n=22). Serum immunoglobulin E (IgE) and thymus and activation-regulated chemokine (TARC/CCL17) were analyzed at baseline and Week 8. Differences between vehicle and each treatment arm were determined using mixed-model repeated measures; significance was conferred at P<0.05. Application of ruxolitinib cream 1.5% BID for 8 weeks significantly (P=0.0095) reduced TARC/CCL17 levels in circulation versus vehicle-treated patients. Additionally, total serum IgE levels were reduced in patients treated with 1.5% ruxolitinib cream (QD or BID). No material differences were observed with 0.15% QD or 0.5% QD ruxolitinib. Efficacy analyses by baseline TARC/CCL17 (≤522 vs >522 pg/mL) and total IgE subgroups (<200 vs ≥200 kU/L) were performed for percentage changes from baseline in Eczema Area and Severity Index (EASI). Levels of TARC/CCL17 and IgE at baseline did not predict ruxolitinib cream treatment response (percentage reductions in EASI). Treatment of patients with AD with ruxolitinib cream inhibited select Th2 biomarkers, suggesting its ability to modulate disease course.