MYCOPHENOLATE MOFETIL TREATMENT REDUCES THE RISK OF TREATMENT ESCALATION DUE TO VASCULAR COMPLICATIONS IN LIMITED CUTANEOUS SYSTEMIC SCLEROSIS: EMULATION OF A TARGET TRIAL FROM ITALIAN RHEUMATOLOGY SOCIETY SPRING REGISTRY

Objective Mycophenolate Mofetil (MMF) use in limited cutaneous systemic sclerosis (lcSSc) is relatively uncommon due to the lower fibrotic burden and the predominance of the vascular complications. In vitro observations and clinical data from transplanted patients suggest a protective effect of MMF on endothelial function. Our aim was to evaluate the reasons for prescribing MMF treatment in patients with lcSSc and its impact on the need for escalation of vascular complication–related treatments during follow-up. Methods LcSSc patients enrolled in the Italian SPRING registry were retrospectively evaluated. All patients treated with MMF were matched to patients not treated with MMF, based on a roll-entry time-dependent propensity score built on demographics, clinical features and baseline treatment. The escalation of vasoactive or vasodilator treatment up to 60 months was defined as the introduction of iloprost, endothelin receptor antagonists, or phosphodiesterase-5 inhibitors on top of the ongoing treatment, due to uncontrolled or newly diagnosed vascular complications. A hazards Cox model was also adopted to quantify the association of MMF treatment with treatment escalation. Results A total of 1,435 lcSSc patients were evaluated, of whom 152 were prescribed MMF (17.1% male; mean age at lcSSc onset 48.7±13.9 years, 54.6% anti-Scl70 positive). The prescription of MMF was more common in 21514658, ja, Downloaded from https://acrjournals.onlinelibrary.wiley.com/doi/10.1002/acr.70039 by Dilia Giuggioli - University Modena , Wiley Online Library on [16/01/2026]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Mycophenolate mofetil and vascular complications of systemic sclerosis males and in anti-Scl70 positive patients, anti-centromere negative, and in patients with interstitial lung disease, myositis, and without a history of digital ulcers. After matching 107 patients with MMF untreated controls, the overall incidence of vasoactive/vasodilator treatment escalation events related to digital ulcers over a median follow-up of 40.5 months (IQR 23.3-60.0) was 0.3 per 100 patient-years in the MMF-treated group and 5.4 per 100 patient-years in the matched control group, with a significant difference in treatment escalation-free survival between the two groups (HR 0.05, 95% CI 0.01-0.38, p-value = 0.004). Conclusions In lcSSc patients, the introduction of MMF has reduced the need for escalation of vasoactive or vasodilator treatment, suggesting that it may also help to prevent vascular complications, which frequently affect patients with lcSSc.