Systemic methotrexate for the treatment of psoriasis

Abstract

In the era of biologic therapies, methotrexate (MTX), a classic immunomodulator, is still the cornerstone of systemic treatment of psoriasis. MTX has been used for many years, achieving good responses with a good safety profile. However, only a few randomized clinical trials have been performed involving MTX, and most of the current evidence comes from pivotal studies of biologic drugs. The aim of this article is to make an extensive review of the MTX mechanism of action, pharmacokinetics, efficacy, safety and tolerability, especially focusing on the future perspective of this old drug and recent advances in the field of pharmacogenetics.

Genetic Influences on Pharmacological Interventions in Psoriasis

“…Methotrexate is a systemic treatment used for a variety of other diseases and has been proven to be a safe and effective option for psoriasis therapy [18]. MTX inhibits dihydrofolate reductase, thus halting dividing cells within the S phase.…”

“…The anti-proliferative effects of MTX make it useful in situations of unwanted rapidly proliferating cells, such as neoplasm. It is also suggested that active circulating T lymphocytes and monocytes are more susceptible to the effects of MTX, which may attribute to its anti-inflammatory effects [18]. MTX can be administered orally, intramuscularly or subcutaneously.…”

“…The biologics used in psoriasis therapy are usually monoclonal antibodies or foreign proteins that target specific mediators in the inflammatory response. Due to their protein structure, they are the target of host immunity and the generation of anti-drug antibodies [18]. The concomitant use of an immunosuppressive, like MTX, along with a biologic, can extend the use and response time while minimizing the production of ADAs [18].…”

“…Due to their protein structure, they are the target of host immunity and the generation of anti-drug antibodies [18]. The concomitant use of an immunosuppressive, like MTX, along with a biologic, can extend the use and response time while minimizing the production of ADAs [18]. However, MTX has its fair share of undesirable side effects, such as gastrointestinal irritation, hepatotoxicity, and hematopoietic suppression [9,18].…”

“…The concomitant use of an immunosuppressive, like MTX, along with a biologic, can extend the use and response time while minimizing the production of ADAs [18]. However, MTX has its fair share of undesirable side effects, such as gastrointestinal irritation, hepatotoxicity, and hematopoietic suppression [9,18]. Up to 30% of individuals discontinue therapy due to these very serious side effects [19].…”