Guidelines developed on dosing, monitoring protocols, managing side effects of methotrexate for pediatric patients | Image Credit: © Halfpoint - © Halfpoint - stock.adobe.com.

Several consensus-based guidelines for the use of methotrexate (MTX) in pediatric inflammatory skin diseases have been developed, according to new findings, filling an unmet need by providing evidence-based recommendations for effective treatment options.¹

These guidelines were developed to address the hesitation clinicians often have when considering off-label methotrexate use in pediatric patients for various inflammatory diseases such as morphea, atopic dermatitis, psoriasis, and alopecia areata.^2,3

The drug is still not approved by the US Food and Drug Administration (FDA), and given this fact and the general lack of robust information on its use, the research was authored by Elaine C. Siegfried, MD, from Saint Louis University's School of Medicine in St. Louis, Missouri.

“The aim of this project was to create evidence-based, consensus-derived, detailed recommendations for long-term management of inflammatory skin diseases in pediatric patients, regardless of physician specialty,” Siegfried and colleagues wrote.

Background and Findings

A panel made up of 23 clinicians with expertise in research and treatment development, including medical dermatologists, pediatric dermatologists, pediatric rheumatologists, and representatives from the FDA, the industry, patient advocacy groups, and research alliance, participated in the consensus process.

The investigators in their committee made guidelines which were evidence- and consensus-based in 5 distinct areas: indications and contraindications, dosing levels, interactions with immunizations and medications, adverse effects and their management, and needs in monitoring.

Each topic of interest was assigned to a specific committee, which all performed an extensive search of literature and later drafted preliminary statements based on the evidence and expert opinions reviewed.

A modified Delphi process utilizing an online survey platform was employed by the investigators, with 100% participation from their panel. Consensus was then defined as ≥70% agreement on a Likert scale, and statements achieving consensus in the original survey were accepted, while those without consensus were modified based on comments and used for another survey.

The key consensus statements were the following:

• Test doses were shown to be unnecessary for initiating low-dose (≤1 mg/kg) methotrexate treatment in pediatric individuals affected by inflammatory skin diseases.
• Abrupt discontinuation of the drug does not typically cause adverse effects, except for an increased risk of disease exacerbation.
• Most pediatric patients receiving treatment for inflammatory skin disease can safely use methotrexate in conjunction with antibiotics (including TMP/S) and NSAIDs.
• Regular surveillance laboratory monitoring, including CBC with differential, ALT, AST, and creatinine, is recommended at baseline, after 1 month of treatment, and every 3 - 4 months thereafter.
• Routine liver biopsy is not required for monitoring pediatric patients on low-dose MTX.
• Transient elevation of transaminase levels (≤3× ULN for <3 months) is commonly observed with low-dose levels of the drug and usually does not necessitate discontinuation. Potential causes include concomitant viral infection, recent methotrexate dosing prior to blood collection, administration of other medications, and recent alcohol consumption.
• Onset of the drug’s efficacy may occur within 8 - 16 weeks.
• Supplementing with folic acid at a daily dose of 1 mg, regardless of weight, is an effective strategy for minimizing gastrointestinal adverse effects associated with methotrexate.
• The typical dosage of the drug varies, but the maximum dose for inflammatory skin disease is generally considered to be 1 mg/kg, not exceeding 25 mg per week.
• Patients given methotrexate can receive live virus vaccine boosters (e.g., VZV and MMR) without contraindications. Insufficient data are available to provide recommendations for or against primary immunization with MMR vaccine in patients taking the drug, and inactivated vaccines should be administered to these patients.

The investigators added that generally, methotrexate offers accessibility, reliability, and the ability to be started or stopped by clinicians and patients as needed without compromising effectiveness during re-exposure.

While long-term safety data was shown to be available for the drug, the research team noted that specific efficacy data in pediatric patients with inflammatory diseases continues to be limited.

“MTX has several decades of real-world use to inform long-term safety, but limited disease-specific efficacy data in pediatric patients,” they wrote. “These guidelines are presented to inform dosing, monitoring, and management of potential side effects of MTX for treatment of pediatric inflammatory skin disease.”

References:

1. Siegfried, EC, Arkin, LM, Chiu, YE, et al. Methotrexate for inflammatory skin disease in pediatric patients: Consensus treatment guidelines. Pediatr Dermatol. 2023; 1- 20. doi:10.1111/pde.15327.
2. Menter A, Gelfand JM, Connor C, et al. Joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the management of psoriasis with systemic nonbiologic therapies. J Am Acad Dermatol. 2020; 82(6): 1445- 1486. doi:10.1016/j.jaad.2020.02.044.
3. Zulian F, Culpo R, Sperotto F, et al. Consensus-based recommendations for the management of juvenile localised scleroderma. Ann Rheum Dis. 2019; 78(8): 1019- 1024. doi:10.1136/annrheumdis-2018-214697.

This article was initially published by our sister publication, HCP Live®.