A new study published in the JAMA Dermatology found mycophenolate mofetil (MMF) treatment response comparable to methotrexate (MTX) in reducing disease activity in juvenile localized scleroderma (JLS). Flare rates were similar between the two therapies, while MMF demonstrated better tolerability. Although MTX is widely used as first-line therapy against JLS, its side effects can limit adherence, particularly in pediatric patients. MMF is an immunosuppressive agent increasingly which is used in other autoimmune conditions, has drawn interest as a possible alternative.The study analyzed data from 114 patients enrolled in the National Registry of Childhood Onset Scleroderma and treated at UPMC Children’s Hospital of Pittsburgh between January 2010 and January 2023. All patients were evaluated and followed by the same physician, helping to ensure consistency in diagnosis and outcome assessment. The patients were included if their disease began before age 18 and they were treated with MTX alone, MMF alone, or a combination of both therapies.Of the total cohort, approximately two-thirds were female, reflecting the known female predominance of the disease. The median age at disease onset was just over 8 years. Most patients (nearly 60%) received MTX monotherapy, while about one-quarter were treated with MMF alone and a smaller group received combination therapy.No meaningful differences were observed among the treatment groups in terms of sex distribution, disease subtype, or initial disease severity as measured by standardized clinical tools. One notable distinction was disease duration, where patients in the MMF group had, on average, lived with JLS for a longer period before starting therapy, a factor the authors accounted for in their statistical models.Clinical outcomes were assessed using the Localized Scleroderma Cutaneous Assessment Tool, a validated measure of disease activity. Across all treatment groups, disease activity declined significantly over time. Statistical modeling demonstrated that improvements were comparable between MTX, MMF, and combination therapy.According to adverse event data detailed in the results table, patients receiving MTX reported substantially higher rates of fatigue and nausea compared with those treated with MMF. Nearly half of MTX-treated patients experienced fatigue, and more than half reported nausea, while these symptoms were uncommon in the MMF group.Overall, these findings suggest that MMF offers similar disease control to MTX with fewer side effects, supporting its consideration as a potential first-line therapy for JLS. However, prospective, randomized noninferiority trials are needed to confirm these findings and inform future treatment guidelines.Source:de Rosas, E. C., Wang, J. C., Zigler, C. K., & Torok, K. S. (2026). Methotrexate and mycophenolate mofetil and clinical response in juvenile localized Scleroderma. JAMA Dermatology (Chicago, Ill.). https://doi.org/10.1001/jamadermatol.2025.5662