What is the role of Methotrexate (MTX) in the treatment of psoriasis?

From the Guidelines

Methotrexate is recommended for the treatment of moderate to severe psoriasis in adults, with a typical starting dose of 7.5 to 25 mg weekly, and can be administered orally or subcutaneously. The dosage can be given as a single dose or in 3 doses over 24 hours 1. It is essential to consider a test dose, especially in patients with impaired kidney function, and to administer folic acid or folinic acid to reduce the incidence of gastrointestinal and hepatic adverse effects 1.

Key Considerations

• Methotrexate is less effective than adalimumab and infliximab for cutaneous psoriasis, but is efficacious for the treatment of psoriatic arthritis, although its efficacy is lower than TNF-inhibitors 1.
• Combination therapy with methotrexate and NB-UVB phototherapy can be considered to enhance efficacy and lower cumulative doses of both treatments 1.
• Liver function test monitoring is recommended every 3 to 6 months, with abnormal elevations prompting a repeat laboratory check in 2 to 4 weeks, and persistent elevations requiring a GI referral 1.

Administration and Monitoring

• Methotrexate can be administered orally or subcutaneously, with the latter often causing fewer gastrointestinal side effects.
• Patients should take folic acid supplements to reduce side effects, but large doses may reduce the efficacy of methotrexate 1.
• Ongoing monitoring includes regular blood tests every 1-3 months, with closer monitoring needed for patients with risk factors such as renal insufficiency or advanced age 1.

Safety and Efficacy

• Methotrexate works by inhibiting dihydrofolate reductase, reducing cell proliferation and inflammation.
• Common side effects include nausea, fatigue, and mouth sores, while serious concerns include liver toxicity, bone marrow suppression, and lung inflammation.
• Methotrexate is contraindicated in pregnancy, liver disease, and with excessive alcohol consumption.
• Improvement typically begins within 4-8 weeks, with maximum benefit seen by 12-16 weeks of treatment.

From the FDA Drug Label

Methotrexate is indicated in the symptomatic control of severe, recalcitrant, disabling psoriasis that is not adequately responsive to other forms of therapy, but only when the diagnosis has been established, as by a biopsy and/or after dermatologic consultation Methotrexate is used to control severe, recalcitrant, disabling psoriasis. The drug is indicated when the diagnosis has been established by a biopsy and/or after dermatologic consultation. It is essential to ensure that a psoriasis “flare” is not due to an undiagnosed concomitant disease affecting immune responses 2.

• Key points:
  • Methotrexate is used for severe psoriasis
  • Diagnosis should be established by biopsy and/or dermatologic consultation
  • Ensure psoriasis “flare” is not due to an undiagnosed concomitant disease
  • Methotrexate is used when psoriasis is not adequately responsive to other forms of therapy 2

From the Research

Methotrexate Dosage and Administration

• The recommended starting dose for methotrexate in patients with no risk factors is 10 to 20mg/wk, with a therapeutic dose of 15mg/wk and a maximum dose of 20mg/wk 3
• Methotrexate dosing regimens vary, with start-doses ranging from 5 to 25 mg/week and dosing schemes including single dose or Weinstein schedule 4
• Folic acid supplementation is recommended by most guidelines, with 10 treatment groups using folic acid in randomized controlled trials 4

Patient Evaluation and Monitoring

• Patients must be evaluated before starting methotrexate to assess suitability of treatment, including consideration of vaccination status and screening for tuberculosis and pregnancy 3
• Noninvasive methods are preferred for monitoring hepatotoxicity, with liver biopsy justified after an initial cumulative dosage of 4g in patients with no risk factors for liver disease 5
• Patients must be carefully selected and the drug administered according to specific guidelines to guard against the development of serious side effects 6

Efficacy and Safety

• Methotrexate has remained the backbone of treatment for moderate to severe psoriasis due to its high efficacy, low cost, and relative ease of administration 7
• Most patients who respond to treatment will show improvement within 8 weeks, with methotrexate being a good treatment option for patients with a history of cancer 3
• However, methotrexate is not recommended in patients with chronic hepatitis B infection or individuals who are seropositive for human immunodeficiency virus 3