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

From the Guidelines

Methotrexate is recommended for the treatment of moderate to severe psoriasis in adults, with a typical starting dose of 7.5-25 mg weekly. The dose can be given as a single dose or in 3 doses over 24 hours 1. It can be administered orally or subcutaneously, with the latter often causing fewer gastrointestinal side effects.

Key Considerations

• Before starting treatment, baseline laboratory tests including complete blood count, liver function, kidney function, and hepatitis screening are essential.
• During treatment, regular monitoring of blood counts and liver function (every 3-6 months) is necessary, with more frequent monitoring for patients with risk factors for hepatotoxicity 1.
• Folic acid supplementation is recommended to reduce the incidence of GI and hepatic adverse effects, although large doses may reduce the efficacy of methotrexate 1.
• Combination therapy with methotrexate and NB-UVB phototherapy can be considered for adult patients with generalized plaque psoriasis to enhance efficacy and lower cumulative doses of both treatments 1.

Administration and Monitoring

• A test dose should be considered, especially in patients with impaired kidney function 1.
• Liver function test monitoring is recommended every 3 to 6 months, assuming there are no laboratory abnormalities in the results, with more frequent monitoring for patients with risk factors for hepatotoxicity 1.
• Noninvasive hepatic specific serology should be performed at baseline and annually thereafter, irrespective of total cumulative dose 1.

Side Effects and Contraindications

• Common side effects include nausea, fatigue, and potential liver toxicity.
• Methotrexate is contraindicated in pregnancy, and both men and women should use effective contraception during and for at least 3 months after treatment.
• Improvement typically begins within 4-8 weeks, with maximum benefit seen by 12-16 weeks of therapy. The most recent and highest quality study supports the use of methotrexate for moderate to severe plaque psoriasis, with a strong recommendation for its use in adults 1.

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 for the treatment of plaque psoriasis.
• The indication is for severe, recalcitrant, disabling psoriasis that is not adequately responsive to other forms of therapy.
• It is essential to establish the diagnosis through biopsy and/or dermatologic consultation before using methotrexate for psoriasis treatment 2.

From the Research

Methotrexate for Plaque Psoriasis

• Methotrexate is one of the most commonly used systemic drugs for the treatment of moderate to severe psoriasis 3.
• The use of an intensified dosing schedule of subcutaneous methotrexate in patients with moderate to severe plaque-type psoriasis has shown a favourable 52 week risk-benefit profile 3.
• A systematic review of the use of test-dose, start-dose, dosing scheme, dose adjustments, maximum dose and folic acid supplementation for methotrexate in plaque-type psoriasis found that there is a range of methotrexate dosing regimens for psoriasis 4.
• Expert recommendations for the use of methotrexate in moderate to severe psoriasis include a starting dose of 10 to 20mg/wk, a therapeutic dose of 15mg/wk, and a maximum dose of 20mg/wk 5.
• Methotrexate is a good treatment option for patients with a history of cancer, but is not recommended in patients with chronic hepatitis B infection or individuals who are seropositive for human immunodeficiency virus 5.
• A practice survey in France found that methotrexate is used by the majority of dermatologists interviewed for moderate to severe psoriasis in adults, with heterogeneity of practices 6.
• The survey also found that 57% of dermatologists use methotrexate as a first line systemic treatment, and 98.7% of dermatologists prescribe folic acid with methotrexate 6.

Dosing Regimens

• The methotrexate start-dose in randomized controlled trials varied from 5 to 25 mg/week, most commonly being either 7.5 mg or 15 mg 4.
• Guidelines vary from 5 to 15 mg/week for the start-dose of methotrexate 4.
• A fixed dose, predefined dose, or dose adjusted on clinical improvement can be used for methotrexate treatment 4.
• Folic acid supplementation is recommended with methotrexate treatment, with 98.7% of dermatologists prescribing folic acid with methotrexate 6.

Comparison with Other Treatments

• A systematic review of indirect clinical trial evidence found that ustekinumab, adalimumab, infliximab, and etanercept can be regarded as clinical equivalents for the treatment of psoriasis, with choice between these agents depending on their relative safety profiles, individual contra-indications, and cost effectiveness 7.