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.