Psoriasis is a chronic immune-mediated skin disease characterized by significant cutaneous and systemic inflammation which negatively affects the quality of life. Specifically, patients with psoriasis have elevated levels of Th17-associated cytokines and increased down-stream signaling in lesional skin and circulating blood. Ruxolitinib cream (Rux Cream) is a potent, topically applied, selective inhibitor of JAK1 and JAK2 of the JAK-STAT signaling pathway. Treatment with Rux Cream was associated with significant therapeutic benefit in patients with mild to moderate psoriasis. This study investigated the effects of Rux Cream on inflammatory mediator expression in circulation. Sera from 22 participants (n=5 0.5% twice daily [BID], n=5 1.5% once daily [QD], and n=12 1.5% BID) in an open-label Phase 2a study (NCT00617994) and 143 participants (n=33 vehicle, n=36 0.5% QD, n=39 1.0% QD, and n=35 1.5% QD) in a dose range–finding Phase 2b study (NCT00778700) were analyzed for broad proteomic changes following treatment. Paired t-tests were used to establish significant changes within treatment groups at a cutoff of p<0.05. Expression of 1010 proteins was evaluated for each participant. In the Phase 2a study, 99 proteins were significantly modulated between baseline and Week 4 (from all 22 participants). In the Phase 2b study, 19 proteins were modulated between baseline and Week 4 in 0.5% QD, 65 proteins in 1.0% QD, and 34 proteins in 1.5% QD compared with 9 proteins in the vehicle cohort. Interestingly, peptidase inhibitor 3 (PI3; elafin, skin-derived antileukoprotease [SKALP]), a potential inflammatory marker in psoriasis, was significantly down-regulated in all Rux Cream treated cohorts across both Phase 2 studies. Additionally, IL-17A and kallikrein-related peptidase 8 (KLK8) levels were significantly reduced in all participants from the Phase 2a study and those treated with 1.5% QD in the Phase 2b study. The results from these studies suggest that topical treatment with Rux Cream has the potential to modulate disease pathogenesis by reducing the circulating levels of disease-related inflammatory markers during the course of treatment.

Ruxolitinib Cream Suppresses Inflammation in Adult Mild to Moderate Psoriasis Patients