Methotrexate Safety in Psoriasis: An Overview

Methotrexate is a highly efficacious treatment for psoriasis, but the use of methotrexate may be limited by concerns regarding its adverse reactions. On average, 28.3 % of patients with psoriasis treated by methotrexate develop adverse reactions. The occurrence of adverse drug reactions in some cases leads to the therapy discontinuation, which may be accompanied by psoriasis exacerbation. The purpose of this article is to provide an extensive review of the methotrexate efficacy, safety and tolerability as well as provide a comprehensive understanding of methotrexate pharmacokinetics and pharmacodynamics, methotrexate side effects pathogenesis, approaches to methotrexate safety monitoring, situations in which it is necessary to be vigilant when prescribing methotexate. We also outline current data concerning methotrexate molecular mechanism of action, including new data on its anti-inflammatory activity, that allow us to explain the pathogenesis of a number of adverse drug reactions, as well as discuss possible ways of predicting the methotrexate toxicity, especially focusing on recent advances in the field of pharmacogenetics of methotrexate-induced toxicity and personalized approach to psoriasis treatment.