What is the recommended dosing regimen for methotrexate (MTX) in the treatment of rheumatoid arthritis or psoriasis?

Methotrexate Dosing Recommendations for Rheumatoid Arthritis and Psoriasis

For both rheumatoid arthritis and psoriasis, methotrexate should be administered at a weekly dosage ranging from 7.5 mg to 25 mg, with individualized titration based on clinical response and tolerability. 1, 2

Initial Dosing Strategy

• A test dose of 2.5-5 mg is recommended before starting full therapy, especially in patients with impaired kidney function or other significant comorbidities 3, 1
• For rheumatoid arthritis, the recommended starting dose is 7.5 mg once weekly, administered intramuscularly with escalation to achieve optimal response 2
• For psoriasis, methotrexate is typically administered in doses ranging from 7.5 mg to 25 mg weekly 1
• Doses can be gradually increased by 2.5-5 mg every 2-4 weeks if needed for disease control 3
• Maximum recommended dose should not ordinarily exceed 25-30 mg per week 1, 3

Administration Routes and Scheduling

• Methotrexate can be administered orally, subcutaneously, or intramuscularly 1
• Weekly dosing is standard practice; daily dosing has shown less benefit and more liver enzyme elevations 1
• For oral administration, the dose can be given as a single weekly dose or divided into 3 doses over 24 hours 1
• Subcutaneous administration may provide higher bioavailability and can be considered if oral therapy is not tolerated 4
• Allow 4 weeks after dose adjustments to assess clinical response before further changes 1, 3

Folate Supplementation

• Folic acid supplementation (1-5 mg daily) is strongly recommended, except on the day of methotrexate administration 1, 3
• Folate supplementation reduces the incidence of gastrointestinal side effects, hepatic abnormalities, and potentially hematologic toxicity 1, 3
• Some evidence suggests that very high doses of folate might slightly reduce methotrexate efficacy, though this remains uncertain 1

Monitoring and Dose Adjustments

• Complete blood count monitoring is recommended every 2-4 weeks initially, then every 1-3 months once stable 1
• Liver function tests should be performed every 3-6 months, assuming there are no laboratory abnormalities 1
• Renal function (BUN, creatinine) should be obtained at 2-3 month intervals 1
• If adverse effects occur, consider dose reduction, splitting the dose, or changing the route of administration 1
• For persistent elevations in liver enzymes (>3x normal), consider dose reduction; if >5x normal, discontinue treatment 1

Comparative Efficacy

• Starting with 15 mg vs. 7.5 mg weekly in rheumatoid arthritis showed similar efficacy at 12 weeks, though nausea was more common with the higher starting dose 5
• Methotrexate is less effective than biologics like adalimumab and infliximab for cutaneous psoriasis but remains first-line therapy due to its favorable risk/benefit ratio 1, 6
• In rheumatoid arthritis, methotrexate is considered the cornerstone of therapy with comparable efficacy to other drugs including anti-TNF therapy at 1 year 7

Common Pitfalls and Caveats

• Avoid methotrexate in pregnancy, nursing mothers, alcoholism, liver disease, immunodeficiency syndromes, and bone marrow hypoplasia 1
• Dosing errors can lead to serious toxicity; ensure patients understand the weekly (not daily) dosing schedule 1
• Drug interactions with hepatotoxic drugs, NSAIDs, and medications that interfere with renal secretion of methotrexate can increase toxicity 1
• Monitor for common adverse effects including nausea, stomatitis, fatigue, and elevated liver enzymes 1
• Serious but less common adverse effects include myelosuppression, hepatotoxicity, and pulmonary fibrosis 1

Methotrexate twice weekly administration has shown no advantage over once weekly regimens in terms of efficacy, supporting the standard once-weekly dosing approach 8.