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.

Keywords:

• adenosine
• dihydrofolate reductase inhibitor
• folic acid
• methotrexate
• methotrexate polyglutamates
• pharmacogenetics
• psoriasis

Financial & competing interests disclosure

L Puig has served as a consultant to Gebro Pharma and Pfizer and has received honoraria for this. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Methotrexate (MTX) remains a fundamental drug in the dermatologists’ therapeutic armamentarium.

• MTX can be used in monotherapy or in combination with biologic drugs and other systemic therapies.

• The combination of MTX and biologics is becoming a generally accepted strategy in the treatment of refractory psoriasis.

• Low-dose weekly regimens of MTX are generally safe when used in carefully selected patients, even for prolonged periods of time.

• Noninvasive techniques are replacing or at least restricting the indication of liver biopsy for evaluation of chronic MTX-associated liver toxicity.

• Pharmacokinetics-based dose customization can be expected to eventually become clinically relevant in patients with psoriasis receiving MTX treatment.

• The advances in pharmacogenomics have been shown to be effective in decreasing hematologic adverse events in patients treated with high-dose MTX and will contribute to improving the tolerance of MTX in patients with psoriasis.

Notes