The wide variety of methotrexate dosing regimens for the treatment of atopic dermatitis: a systematic review

Abstract

Background:

Methotrexate is an off-label therapy for atopic dermatitis. A lack of consensus on dosing regimens poses a risk of underdosing and ineffective treatment or overdosing and increased risk of side effects. This systematic review summarizes the available evidence on dosing regimens.

Materials and methods:

A literature search was conducted, screening all randomized controlled trials (RCTs) and guidelines published up to 6 July 2023, in the MEDLINE, Embase, and Cochrane Library databases.

Results:

Five RCTs and 21 guidelines were included. RCTs compared methotrexate with other treatments rather than different methotrexate dosing regimens. The start and maintenance doses in RCTs varied between 7.5–15 mg/week and 14.5–25 mg/week, respectively. Despite varied dosing, all RCTs demonstrated efficacy in improving atopic dermatitis signs and symptoms. Guidelines exhibited substantial heterogeneity but predominantly proposed starting doses of 5–15 mg/week for adults and 10–15 mg/m²/week for children. Maintenance doses suggested were 7.5–25 mg/week for adults and 0.2–0.7 mg/kg/week for children. One guideline suggested a test dose and nearly half advised folic acid supplementation.

Conclusion:

This systematic review highlights the lack of methotrexate dosing guidelines for atopic dermatitis. It identifies commonly recommended and utilized dosing regimens, serving as a valuable resource for clinicians prescribing methotrexate off-label and providing input for an upcoming consensus study.

Keywords:

• Atopic dermatitis
• atopic eczema
• treatment
• dosing
• methotrexate
• systematic review

Author contributions

Conceptualization: P.I. Spuls, am van Huizen, and A.G.M. Caron; literature search: N.P. Denswil; study selection and data extraction: M. Bloem, H. El Khattabi, A.C. de Waal, and A.G.M. Caron; data analysis: M. Bloem and A.G.M. Caron; supervision: P.I. Spuls and L.A.A. Gerbens. The first draft of the manuscript was written by A.G.M. Caron and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Disclosure statement

P.I. Spuls received departmental independent research grants for the TREAT NL registry from Pharma since December 2019. She is engaged in conducting clinical trials with several pharmaceutical industries producing drugs for treating conditions such as psoriasis and atopic dermatitis. Compensation is provided to the department/hospital for these endeavors. She is Chief Investigator (CI) of the systemic and phototherapy atopic eczema registry (TREAT NL) for adults and children. P.I. Spuls is one of the authors of three of the included follow-up RCTs: Gerbens et al. Schram et al. and Roekevisch et al. P.I. Spuls and L.A.A. Gerbens made contributions to one of the included guidelines authored by Aoki et al. L.A.A. Gerbens is one of the main investigators of the TREAT NL registry. She is the first author of one of the included RCTs: Gerbens et al. and is an author of the EuroGuiDerm guideline authored by Wollenberg et al. A.G.M. Caron and am van Huizen served as a subinvestigators in clinical trials and observational studies for AbbVie and Janssen and as a subinvestigators for the TREAT NL registry.

Additional information

Funding

No funding or sponsorship was received for this study or publication of this article.