866 Baseline differences in circulation between early vs late responder patients with vitiligo treated with ruxolitinib cream

Abstract

Vitiligo is a chronic, inflammatory skin disease characterized by increased interferon-gamma signaling through Janus kinase (JAK) 1 and JAK2 and subsequent activation of CD8+ T cells, which target melanocytes resulting in areas of depigmentation. Ruxolitinib cream, a JAK1/JAK2 inhibitor, is under investigation for vitiligo treatment in a 52-week, randomized, double-blind, phase 2 study (NCT03099304). Significantly more patients treated with ruxolitinib cream vs vehicle achieved ≥50% improvement in facial Vitiligo Area Scoring Index (F-VASI50) at Week 24 (primary endpoint); at Week 52, patients treated with ruxolitinib cream 1.5% twice daily (BID) attained the highest F-VASI50 response (57.6%). This analysis investigated the differences between early and late responders (ER and LR, respectively) following treatment with ruxolitinib cream. Patients were classified as ER if they achieved F-VASI50 or greater at Week 24; all other patients were classified as LR. In ER, F-VASI improved by 79.9%±4.0% and 91.9%±1.5% at Weeks 24 and 52, respectively. In contrast, F-VASI improved by 1.1%±7.3% and 25.1%±13.4% in LR at Weeks 24 and 52. Broad serum proteomics of 54 patients identified 76 out of 1104 proteins were differentially expressed between ER and LR at baseline at p < 0.05. Eleven proteins were up-regulated in ER while the rest were down-regulated in ER. Overall, this analysis identified significant differences between ER and LR that require deeper scientific interrogation and may be important in stratifying the therapeutic benefit for patients with vitiligo.