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

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. 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. 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/m /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. 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.