Long-Term Efficacy of Methotrexate Demonstrated in Pediatric Linear Scleroderma

Researchers evaluated disease course and long-term efficacy of methotrexate treatment in children with linear scleroderma.

Patients treated with methotrexate (MTX) for pediatric linear scleroderma may achieve complete and long-lasting remission, according to research results published in Arthritis Care & Research. Study findings showed that longer treatment duration with MTX correlated with a greater likelihood of sustained remission.

Investigators evaluated treatment response and remission rates in patients treated with MTX for linear scleroderma at a single pediatric rheumatology center in Italy. Eligible participants had received treatment with MTX for >1 year and had ≥2 years of follow-up data. Disease activity was measured at baseline using the Localized Scleroderma Skin Severity Index and infrared thermography. Remission was defined by characteristics including the absence of new lesions, existing lesion enlargement, and erythema, skin thickening, and hyperthermia on thermography. Researchers used the Kaplan-Meier method to calculate relapse-free survival in the total cohort. Logistic regression was performed to identify predictors of remission.   

The study cohort included 50 patients, among whom 31 (62%) were girls. Mean age at disease onset was 7.1 years; mean age at diagnosis was 8.5 years. A majority of patients (72%) had linear scleroderma with unilateral involvement; 24 (48%) had linear scleroderma of the trunk and/or limbs and 26 (52%) of the face/head. Tissue damage was mild in 42% of patients, moderate in 32%, and severe in 26%. Mean MTX treatment duration was 3.1 years (range, 1.8-8.5 years). During follow-up, 42 patients (84%) responded to full-dose MTX, of whom 34 did not experience any flares and 8 (19%) experienced at least 1 flare. Flares were treated with single-dose prednisone or an additional full course of MTX. Among the 8 nonresponders, prednisone or mycophenolate mofetil was added to MTX to achieve treatment response. Overall, MTX was well tolerated; 5 patients reported mild gastrointestinal symptoms and 3 experienced increases in transient liver enzymes. 

According to the Kaplan-Meier curves, the probability of being in remission at 30 months follow-up was 90%. In analyses stratified by follow-up time, complete remission was observed in 18.2%, 80.0%, and 87.5% of patients with 2 to 5 years, 6 to 10 years, and >10 years of follow-up, respectively. Logistic regression analyses indicated that therapy duration was inversely correlated with likelihood of disease relapse (P <.05) and severity of tissue damage (P <.005).

Overall, results from the cohort study support the long-term efficacy of MTX therapy for children with linear scleroderma, with earlier diagnosis and longer treatment duration appearing to be critical for maintaining remission.

Study limitations included the small sample size, use of a single clinic, and the fact that data may not be generalizable to other populations.

“[Our] study adds significant data regarding the long-term [outcomes] of juvenile [linear scleroderma] treated with MTX as first-line agent,” the investigators wrote. “The long-term monitoring of patients, even after therapy withdrawal, is crucial to promptly identify possible flares and treat them adequately.”


Fadanelli G, Agazzi A, Vittadello F, Meneghel A, Zulian F, Martini G. Methotrexate in linear scleroderma: long-term efficacy in 50 children from a single pediatric rheumatology centre [published online May 20, 2020]. Arthritis Care Res (Hoboken). doi:10.1002/acr.24260