A RETROSPECTIVE cohort study has found that mycophenolate mofetil (MMF) demonstrates similar clinical effectiveness to methotrexate (MTX) in the treatment of juvenile localised scleroderma (JLS), while being associated with significantly fewer adverse effects. The findings suggest MMF may represent a viable alternative first-line therapy for this rare paediatric autoimmune condition.
Therapeutic Options for Juvenile Localised Scleroderma
Juvenile localised scleroderma is a rare paediatric inflammatory disorder associated with progressive skin fibrosis and potential functional impairment. In the absence of US Food and Drug Administration–approved therapies for juvenile localised scleroderma, methotrexate has become established as off-label first-line treatment in routine clinical practice. However, treatment-limiting adverse effects may compromise adherence, prompting interest in alternative immunosuppressive agents such as MMF.
The study analysed data from 114 patients with clinician-diagnosed JLS enrolled in the National Registry of Childhood Onset Scleroderma and treated at UPMC Children’s Hospital of Pittsburgh between 2010 and 2023. Patients were managed with MTX monotherapy, MMF monotherapy, or combination therapy, and all were assessed using standardised clinical outcome measures by the same physician.
Comparable Reductions in Disease Activity Across Treatments
Across all treatment groups, disease activity scores showed statistically significant reductions over time, with no meaningful differences in the magnitude of improvement between MTX and MMF. Rates of disease flare during follow-up were also comparable, indicating similar effectiveness in achieving and maintaining disease control.
Crucially, the tolerability profiles differed significantly. Patients receiving MTX experienced substantially higher rates of fatigue and nausea compared with those treated with MMF, highlighting a potential quality-of-life advantage for MMF in long-term management. These differences may have important implications for treatment adherence in paediatric populations, where medication tolerability plays a critical role in sustained disease control.
The authors conclude that MMF demonstrates comparable clinical response to MTX in reducing disease activity and maintaining inactive disease in JLS, with improved tolerability. While the study is retrospective in design, the findings provide clinically meaningful evidence supporting MMF as a potential first-line therapeutic option.
Future Directions for Clinical Trials
The researchers emphasise the need for prospective, randomised noninferiority trials to confirm these results and inform future treatment guidelines. If validated, MMF could offer clinicians greater flexibility in personalised treatment selection and improve long-term outcomes for children living with juvenile localised scleroderma.
Reference
de Rosas EC et al. Methotrexate and Mycophenolate Mofetil and Clinical Response in Juvenile Localized Scleroderma. JAMA Dermatol. 2026;doi:10.1001/jamadermatol.2025.5662.
