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A recently published systematic review was designed as a resource for prescribing methotrexate off-label for patients with atopic dermatitis (AD).

The review, which appears in the , included data from five randomized clinical trials (RCT) and 21 guidelines. Start and maintenance doses in RCTs varied between 7.5-15 mg per week for starting dose and 14.5-25 mg per week for maintenance doses. All RCTs demonstrated efficacy for methotrexate in improving AD, researchers wrote.

Guidelines were heterogeneous but predominantly proposed starting doses of 5-15 mg per week for adults and 10-15 mg/m² per week for children. Suggested maintenance doses were 7.5-25 mg per week for adults and 0.2-0.7 mg/kg per week for children.

First author Anouk Caron, MD, PhD, is a dermatologist and researcher with the University of Amsterdam in The Netherlands. Caron's exchange with the Reading Room has been edited for length and clarity.

What was the motivation for this review and what were its objectives?

Caron: The primary motivation was to improve methotrexate treatment for AD, as it remains a relevant option due to its affordability and accessibility compared to newer targeted therapies.

The review aimed to evaluate the current evidence surrounding methotrexate dosing in AD, focusing on regimens used in randomized clinical trials and the recommendations outlined in clinical guidelines. Another objective was to lay the groundwork for establishing a future international consensus on methotrexate dosing for AD.

How do you intend for this paper to help or serve as a resource for dermatologists?

Caron: Ideally, we would have RCTs that directly compare different dosing regimens, but the reality is that these trials do not exist yet and likely never will because of a lack of financial incentive. Given this, we believe that creating an overview of the current knowledge is the next best approach.

This review provides dermatologists with insights into methotrexate dosing regimens for AD. By analyzing current dosing strategies in both clinical trials and guidelines, it supports clinicians in making more informed treatment decisions. It serves as a reference for those seeking a suitable methotrexate dosing regimen for their patients.

What were your key findings?

Caron: Despite differences in dosing regimens, all RCTs included in the review showed that methotrexate effectively reduces AD symptoms.

The review identified variability and inconsistency in methotrexate dosing regimens for AD. Although various dosing strategies were effective in improving AD symptoms, the heterogeneity of randomized clinical trials made it challenging to determine the most optimal approach.

Despite this, the review does highlight the most frequently used and guideline-recommended dosing regimens.

What are the take-home messages?

Caron: The review outlines the most commonly used and recommended dosing regimens, offering a practical overview for clinicians. Special attention should be given to discussing dosing schedules with patients, particularly when doses are divided over multiple days, to avoid potential errors.

The report notes that there may be global implications for this line of research. What are those potential implications?

Caron: Given methotrexate's widespread availability, optimizing its dosing regimen could have a global impact, by raising the standard of care for patients with AD.