Methotrexate Update: Mechanism of Action in Psoriasis Therapy

Background Long before the advent of the biologic agents, methotrexate was the gold standard for the treatment of moderate to severe psoriasis. Although methotrexate's therapeutic efficacy in the treatment of psoriasis is well-established, the mechanism of action is still poorly understood. Objective This paper reviews the published research on methotrexate's mechanism of action in psoriasis. Methods Studies published with English abstracts between January 1970 and December 2006 identified in MEDLINE with the keywords methotrexate, psoriasis and mechanism were reviewed. Results Methotrexate appears to exert clinical efficacy in psoriasis by interfering with CLA+ T-cell infiltration into lesional skin via multiple mechanisms. Conclusion It is likely that methotrexate interferes with the inflammatory pathways critical to psoriasis pathogenesis by multiple mechanisms. Current evidence suggests that methotrexate works by decreasing the number of circulating CLA+ T cells; decreasing inflammatory infiltrate into the dermis and epidermis by downregulating adhesion molecules in endothelial cells; and downregulating the expression of adhesion molecules on T cells.