Methotrexate in Atopic Dermatitis: Experts Clarify Dosage

Methotrexate (MTX) is a commonly used treatment option for managing refractory atopic dermatitis, especially as an alternative to cyclosporine, anti-interleukins, or anti-JAK treatments. According to the 2022 European EuroGuiDerm guideline, this immunomodulator is “moderately effective, relatively safe, and well-tolerated” for severe atopic dermatitis both in adults and children. However, due to the lack of randomized clinical trials, dosing guidelines remain somewhat unclear. Currently, recommended initial doses range from 5 to 15 mg/wk for adults (up to a maximum of 25 mg/wk) and from 0.3 to 0.4 mg/wk for children.

Although MTX is frequently considered by dermatologists for treating atopic dermatitis that does not respond to topical treatments, real-world dosing practices vary widely. To address this variability, a global panel of around 100 dermatology experts used the Delphi method to establish consensus on recommendations to guide clinical practice and standardize MTX use.

Key recommendations for adults and children included the following points:

• MTX should be administered once weekly, not divided throughout the week.
• Treatment should continue for at least 8-12 weeks before evaluating effectiveness.
• Dose increases should be gradual, such as 2.5-5 mg/wk, with evaluations every 2-3 months.
• If oral MTX proves ineffective after 8-12 weeks, switching to subcutaneous administration may be considered before stopping treatment.
• Gastrointestinal side effects can be mitigated by switching to subcutaneous dosing from oral administration or splitting the dose over 2 days.
• MTX treatment can be stopped abruptly without the need for tapering.
• There is no maximum treatment duration as long as MTX is well-tolerated and effective.
• Monitoring cumulative MTX dosage is unnecessary in routine clinical practice.
• Patients should receive 5-6 mg of folic acid weekly during MTX therapy, either as a single dose or split into daily doses.

The panel’s specific recommendations for adults included the following points:

• There’s no requirement for a test before starting MTX.
• Typically, treatment begins at 15 mg/wk, with adjustments made based on factors such as renal function or age.
• The maximum dose for MTX in adults is 25 mg/wk.

Its specific recommendations for children included the following points:

• Like adults, children do not require a test dose at the start of treatment.
• MTX should be dosed based on the child’s weight (mg/kg).
• The recommended starting dose ranges from 0.2 to 0.4 mg/kg/wk.
• The dose should not exceed 0.7 mg/kg/wk, with a maximum cap of 25 mg/wk.

The authors noted that some points, such as the route of administration and dose fractioning for managing gastrointestinal side effects, sparked a more thorough debate. Although oral administration was initially favored, the final consensus remained neutral between oral and subcutaneous routes. Regarding dose fractioning, the risk of dosing errors prompted the group to emphasize the importance of clear communication with patients to prevent mistakes.

The recommendations largely align with those for other inflammatory skin diseases, although the maximum dose for pediatric atopic dermatitis is slightly lower. The lack of a clear preference for administration routes may stem from insufficient data, as oral administration is often favored in psoriasis treatment. Ultimately, clinicians should base their decisions on the patient’s unique profile, characteristics, and preferences.

This story was translated from Univadis France using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.