Vitiligo Biomarker CXCL10 Correlates With Clinical Response to Ruxolitinib Cream in the Phase 2 Randomized TRuE-V Mechanism-of-Action Study

TRIAL DESIGN: This phase 2, randomized, double-blind, vehicle-controlled trial investigated the mechanism of action of ruxolitinib cream in vitiligo. METHODS: Adults with vitiligo were randomized 2:1 to twice-daily 1.5% ruxolitinib cream (n=41) or vehicle (n=19) for 24 weeks, after which they applied twice-daily ruxolitinib cream through Week 52. RESULTS: Analyses showed significant downregulation of serum proteins related to interferon-gamma (IFN-γ), including IFN-γ-inducible C-X-C motif chemokine ligand 10 (CXCL10) at all post-ruxolitinib cream time points (P<0.05; fold change >1.25). In sera and lesional skin, CXCL10 expression was significantly reduced from baseline at Weeks 12 through 40 (P<0.05). Among patients applying ruxolitinib cream, mean percentage reductions from baseline were significant at Weeks 12 and 24 for facial Vitiligo Area Scoring Index (F-VASI: -32.9%; P<0.01/-49.1%; P<0.001) and Week 24 for total VASI (T-VASI; -21.2%; P<0.05). Reduced CXCL10 expression in sera and lesional skin significantly correlated with T-VASI improvement (P<0.05/P<0.001). Additionally, following 24 weeks of ruxolitinib cream treatment, increases in SOX10+ melanocyte counts significantly correlated with F-VASI improvements (P<0.05). CONCLUSIONS: These data confirm a role for the IFN-γ-CXCL10 axis in vitiligo pathogenesis and suggest that reductions in CXCL10 expression correlate with clinical repigmentation with ruxolitinib cream (clinicaltrials.gov: NCT04896385).