Methotrexate for inflammatory skin disease in pediatric patients: Consensus treatment guidelines

Abstract

Methotrexate (MTX) is a readily accessible drug, first used in 1948 and employed for a wide variety of indications since then. However, despite widespread off‐label use, FDA labeling does not include approved indications for the use of MTX for many inflammatory skin diseases in pediatric patients, including morphea, psoriasis, atopic dermatitis, and alopecia areata, among others. Without published treatment guidelines, some clinicians may be hesitant to use MTX off‐label, or uncomfortable prescribing MTX in this population. To address this unmet need, an expert consensus committee was convened to develop evidence‐ and consensus‐based guidelines for use of MTX to treat pediatric inflammatory skin disease. Clinicians with experience and expertise in clinical research, drug development, and treating inflammatory skin disease in pediatric patients with MTX were recruited. Five committees were created based on major topic areas: (1) indications and contraindications, (2) dosing, (3) interactions with immunizations and medications, (4) adverse effects (potential for and management of), and (5) monitoring needs. Pertinent questions were generated and addressed by the relevant committee. The entire group participated in a modified Delphi process to establish agreement on recommendations for each question. The committee developed 46 evidence‐ and consensus‐based recommendations, each with >70% agreement among members, across all five topics. These are presented in tables and text, along with a discussion of supporting literature, and level of evidence. These evidence‐ and consensus‐based recommendations will support safe and effective use of MTX for the underserved population of pediatric patients who may benefit from this valuable, time‐honored medication.

Methotrexate therapy for adult and paediatric moderate‐to‐severe atopic dermatitis: A PRISMA‐compliant meta‐analysis of data from daily practice

“…We found that the risks of AEs were higher in children compared to adults (Table 3), which reflected higher AEs incidence rates in this population. In fact, high‐incidence rates (as high as 25–50%) for the same adverse effects were reported when safety data of studies using MTX for inflammatory skin diseases in the paediatric population were pooled 44 . Besides, we found that children had a seven‐fold lower rate of treatment discontinuation due to side effects compared to adults, which indicates that the AEs did not call for MTX termination.…”

“…In fact, high-incidence rates (as high as 25-50%) for the same adverse effects were reported when safety data of studies using MTX for inflammatory skin diseases in the paediatric population were pooled. 44 Besides, we found that children had a seven-fold lower rate of treatment discontinuation due to side effects compared to adults, which indicates that the AEs did not call for MTX termination. For example, the increases in transaminases levels observed in the studies for children [37][38][39][40] predominantly had a mild/transient nature or the 11 haematologic abnormalities observed in the paediatric study of reference 37 were transient (see footnotes of Table 2).…”

Treatment with Methotrexate in Infants and Toddlers with Atopic Dermatitis: A Retrospective Multi-Center Study

“…Since information regarding doses and monitoring in infants and toddlers with AD is sparse, we compared our data with the consensus treatment guidelines for MTX in pediatric patients with inflammatory skin diseases [ 27 ]. Nevertheless, this consensus does not provide specific dosage recommendations for AD in pediatric patients, and a starting dosage ranging from 0.3 to 0.5 mg/kg was recommended along with a maintenance dose of less than 1 mg/kg/week.…”

An Overview of Methotrexate Indications in Skin Diseases

“…There are a number of relative or absolute contraindications regarding the administration of MTX that we present in Table 2 [31].…”