Mycophenolate mofetil demonstrated similar effectiveness to methotrexate in reducing disease activity in juvenile localized scleroderma while causing significantly fewer adverse effects, according to a study.
In a retrospective cohort study of 114 patients with juvenile localized scleroderma (JLS), researchers compared outcomes among those treated with methotrexate (MTX) monotherapy, mycophenolate mofetil (MMF) monotherapy, or combination therapy. All three groups achieved inactive disease status within 12 months, with no statistically significant differences in the rate or magnitude of improvement between MTX and MMF.
However, tolerability differed markedly between therapies. Patients treated with MTX experienced significantly higher rates of nausea (60% vs 7%), fatigue (47% vs 11%), anxiety (29% vs 7%), and anticipatory vomiting (18% vs 0%) compared with those receiving MMF.
"These initial findings support MMF as a potential candidate for first-line treatment of JLS," wrote Elena C. de Rosas, BS, of the University of Pittsburgh, and colleagues.
The study analyzed data from patients enrolled in the National Registry of Childhood Onset Scleroderma at a single pediatric center between January 2010 and January 2023. All patients had disease onset prior to age 18 years, and all clinical evaluations were performed by the same physician using the Localized Scleroderma Cutaneous Assessment Tool. Disease activity was measured with the modified Localized Scleroderma Skin Severity Index (mLoSSI).
Of the 114 patients, 68 received MTX, 28 received MMF, and 18 received combination therapy. Baseline demographic characteristics, disease subtype, and disease activity scores were similar across groups, although patients in the MMF group had longer disease duration (median 5.6 years vs 1.5 years) and higher physician-assessed damage scores at treatment initiation.
Longitudinal changes in disease activity were analyzed using linear mixed-effects models that accounted for repeated measures and included covariates such as age at disease onset, disease duration, disease subtype, and corticosteroid use. Because disease activity frequently plateaued at zero once remission was achieved, researchers applied additional modeling strategies to better characterize pre-remission disease trajectories.
Disease flare occurred in 25% of patients overall, with no significant differences in flare-free survival between treatment groups. Following corticosteroid discontinuation, disease activity remained stable across all groups.
The researchers acknowledged several limitations, including the retrospective, nonrandomized design and unequal treatment group sizes. MMF was frequently initiated following longer disease duration or after MTX intolerance or flare, potentially influencing comparative response estimates. Adverse effects were assessed through clinical interviews rather than validated patient-reported measures. The study was not powered to detect small differences in efficacy.
"Prospective, randomized, noninferiority trials are warranted to confirm these results and guide future treatment recommendations," the researchers wrote.
Disclosures can be found in the study.
Source: JAMA Dermatology
