Oral glucocorticoids for skin fibrosis in early diffuse systemic sclerosis: a target trial emulation study from the European Scleroderma Trials and Research group database

OBJECTIVES The objective of this study is to evaluate whether adding oral glucocorticoids to immunosuppressive therapy improves skin scores and ensures safety in patients with early diffuse cutaneous systemic sclerosis (dcSSc). METHODS We performed an emulated randomized trial comparing the changes from baseline to 12±3 months of the modified Rodnan skin score (mRSS: primary outcome) in early dcSSc patients receiving either oral glucocorticoids (≤20 mg/day prednisone-equivalent) combined with immunosuppression (treated), or immunosuppression alone (controls), using data from the European Scleroderma Trials and Research Group. Secondary endpoints were the difference occurrence of progressive skin or lung fibrosis, and scleroderma renal crisis. Matching propensity score was used to adjust for baseline imbalance between groups. RESULTS We matched 208 patients (age 49 years; 33% male; 59% anti-Scl70), 104 in each treatment group, obtaining comparable characteristics at baseline. In the treated group, patients received a median prednisone dose of 5 mg/day. Mean mRSS change at 12±3 months was similar in the two groups (decrease of 2.7 [95% CI 1.4 - 4.0] in treated vs. 3.1 [95% CI 1.9 - 4.4] in control, p = 0.64). Similar results were observed in patients with shorter disease duration (≤ 24 months) or with mRSS ≤22. There was no between-group difference for all prespecified secondary outcomes. A case of scleroderma renal crisis occurred in both groups. CONCLUSIONS We did not find any significant benefit of adding low-dose oral glucocorticoids to immunosuppression for skin fibrosis, and at this dosage, glucocorticoid did not increase the risk of scleroderma renal crisis.