What are the guidelines for prescribing and monitoring Methotrexate (MTX) for psoriasis?

From the Guidelines

Methotrexate for psoriasis should be prescribed at an initial dose of 7.5-15mg once weekly, with gradual titration up to 25mg weekly as needed for efficacy and tolerability, as recommended by the joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the management of psoriasis with systemic nonbiologic therapies 1.

Key Considerations

• Before starting treatment, baseline laboratory tests should include complete blood count, liver function tests, renal function tests, hepatitis B and C screening, and pregnancy testing in women of childbearing potential.
• Folic acid supplementation (1-5mg daily except on methotrexate day) should be prescribed to reduce side effects, as it is recommended to reduce the incidence of GI and hepatic adverse effects 1.
• Monitoring requires regular laboratory testing: complete blood count, liver and renal function tests weekly for the first month, then every 2-4 weeks for the next 2-3 months, and every 1-3 months thereafter.
• Clinical response typically begins within 4-8 weeks, with maximum benefit seen by 3-6 months.
• Methotrexate works by inhibiting dihydrofolate reductase, reducing DNA synthesis and cell proliferation, while also having anti-inflammatory effects.
• Common side effects include nausea, fatigue, mouth sores, and potential liver toxicity.
• Consider liver biopsy after a cumulative dose of 3.5-4g or if liver function tests remain persistently abnormal.
• Methotrexate is contraindicated in pregnancy, significant liver disease, severe renal impairment, and active infection.
• Alcohol consumption should be minimized or avoided during treatment.

Administration and Dosing

• Methotrexate can be administered orally or subcutaneously, with the oral route being preferred by most dermatologists and patients 1.
• The dose can be given as a single dose or in 3 doses over 24 hours, with some patients tolerating the gastrointestinal adverse effects better when the dose is divided into 3 doses 1.
• A test dose should be considered, especially in patients with impaired kidney function, to gauge individual susceptibility to bone marrow suppression 1.

Monitoring and Safety

• Liver function test monitoring is recommended every 3 to 6 months, assuming there are no laboratory abnormalities in the results, with abnormal elevations prompting a repeat laboratory check in 2 to 4 weeks 1.
• For patients with risk factors for hepatotoxicity, it may be reasonable to consider an alternative therapy to methotrexate, or to monitor liver function more closely if methotrexate is chosen 1.
• Noninvasive hepatic specific serology should be performed at baseline and annually thereafter, irrespective of total cumulative dose 1.

From the Research

Prescribing Methotrexate for Psoriasis

• The recommended starting dose for methotrexate in patients with no risk factors is 10 to 20mg/wk, with the therapeutic dose for most patients being 15mg/wk and the maximum dose being 20mg/wk 2.
• Parenteral administration of methotrexate is desirable when there is a risk of erroneous dosing, nonadherence, gastrointestinal intolerance, or inadequate response to the therapeutic dose taken orally 2.
• Methotrexate dosing regimens can vary, with some studies using a test-dose, and guidelines recommending a start-dose of 5 to 15 mg/week 3.
• Folic acid supplementation is recommended by most guidelines, with some studies using it to reduce the risk of hepatotoxicity 3.

Monitoring Methotrexate Therapy

• Routine liver biopsies are not necessary for patients with no risk factors for liver disease on long-term, low-dosage (<20mg), once-weekly methotrexate, with liver biopsy justified after an initial cumulative dosage of 4g 4.
• Non-invasive methods are preferred for monitoring hepatotoxicity, with advances in the non-invasive assessment of liver fibrogenesis potentially reducing the need for biopsy 2, 4.
• Patients should be monitored for treatment response using the Psoriasis Area and Severity Index (PASI) score, and for the development of any adverse effects 5.

Dose Adjustments and Combination Therapy

• The doses of methotrexate can be tapered by reducing the maintenance dose or increasing the between-dose intervals, but should not be discontinued for psoriasis patients with low disease activity 6.
• Combination therapy using pulse azathioprine and low-dose methotrexate can be an efficacious treatment for moderate-to-severe plaque psoriasis, with a relatively good safety profile 5.
• Dose adjustments should be made based on clinical improvement, with a fixed dose, predefined dose, or dose adjusted on clinical improvement used in different studies 3.