Methotrexate Mechanism of Action in Plaque Psoriasis: Something New in the Old View.

Background: Despite the era of biologic therapy in the management of psoriasis, methotrexate, the traditional backbone of psoriasis treatment, does not stop surprising us with what it can offer. Objective: In this study, we aimed to evaluate the peripheral expression and the serum levels of TWEAK in patients with psoriasis vulgaris before and after receiving methotrexate treatment. Methods: The study included 58 patients with moderate to severe psoriasis vulgaris, and 90 apparently healthy individuals as a control group. Before starting the treatment course, all patients were evaluated clinically using Psoriasis Area Severity Index (PASI) score and were subjected to TWEAK serum levels and peripheral expression measurement using ELISA and qRT-PCR techniques, respectively. After 12 weeks of treatment with methotrexate (intramuscular methotrexate; up to 30mg per week) the patients were re-evaluated both clinically and in the laboratory. Results: The baseline serum TWEAK levels and its peripheral mRNA expression in the patients group were significantly lower than those in the control group. After 12 weeks of treatment with methotrexate, the PASI scores were reduced significantly while the serum TWEAK levels and its peripheral expression were significantly elevated. Conclusion: Enhancing TWEAK expression and elevating its serum levels in psoriasis patients seems to be a newly observed mechanism of action of methotrexate.