Methotrexate and Mycophenolate Mofetil and Clinical Response in Juvenile Localized Scleroderma

Importance: Currently, there are no treatments approved by the US Food and Drug Administration for juvenile localized scleroderma (JLS), a rare disease. While methotrexate (MTX) is regularly used as a first-line therapy, emerging data from case series and applications in systemic sclerosis suggest that mycophenolate mofetil (MMF) may be clinically comparable, with potential benefits in tolerability and adherence. Objective: To compare clinical outcomes of patients with JLS treated with MTX and MMF using standardized clinical outcome measures. Design, Setting, and Participants: This retrospective cohort study of patients with clinician-diagnosed JLS who were enrolled in the National Registry of Childhood Onset Scleroderma was conducted at UPMC Children's Hospital of Pittsburgh. Data were from January 2010 to January 2023 and first analyzed in April 2023. All patients were evaluated and followed up by the same physician. Patients were included if they had disease onset before age 18 years and a localized scleroderma diagnosis and enrollment in the National Registry of Childhood Onset Scleroderma before age 21 years. Patients were required to be receiving MTX monotherapy, MMF monotherapy, or combination therapy (CT) of the 2 for their localized scleroderma. Exposures: Patients were treated with MTX, MMF, or CT as prescribed by the examining physician. Main Outcomes and Measures: This study measured comparative medication treatment response through associations with disease activity, as measured using the Localized Scleroderma Cutaneous Assessment Tool. Results: Of 114 patients, 77 (67.5%) were female, and the median (IQR) age at onset was 8.3 (5.4-11.2) years. The MTX, MMF, and CT groups included 68 (59.6%), 28 (24.6%), and 18 patients (15.8%), respectively. There were no significant differences in baseline demographic characteristics, disease subtype, or disease severity between groups, but patients in the MMF group had longer disease duration. Mixed-effects modeling showed statistically significant decreases in activity across all groups (β = -0.14; 95% CI, -0.62 to 0.33). A Kaplan-Meier analysis showed no significant difference in disease flare rate over the follow-up interval (hazard ratio, 0.85; 95% CI, 0.51-1.33). However, patients treated with MTX compared with those treated with MMF had significantly higher rates of fatigue (47% vs. 11%, P = .001) and nausea (60% vs. 7%; P = .001). Conclusions and Relevance: The study results suggest that MMF demonstrated a similar response to treatment as MTX in reducing disease activity in JLS, with comparable flare rates and improved tolerability. These initial findings support MMF as a potential candidate for first-line treatment of JLS. Prospective, randomized, noninferiority trials are warranted to confirm these results and guide future treatment recommendations.