{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T15:21:22Z","timestamp":1787757682315,"version":"build-2784847793"},"reference-count":26,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis Care &amp;amp; Research"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Mycophenolate mofetil (MMF) use in limited cutaneous systemic sclerosis (lcSSc) is relatively uncommon because of the lower fibrotic burden and the predominance of 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\u2013related treatments during follow\u2010up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients with lcSSc enrolled in the Italian Systemic Sclerosis Progression Investigation registry were retrospectively evaluated. All patients treated with MMF were matched to patients not treated with MMF, which was based on a roll\u2010entry time\u2010dependent 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\u20105 inhibitors on top of the ongoing treatment, because of uncontrolled or newly diagnosed vascular complications. A hazards Cox model was also adopted to quantify the association of MMF treatment with treatment escalation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 1,435 patients with lcSSc were evaluated, of whom 152 were prescribed MMF (17.1% male; mean age at lcSSc onset 48.7\u2009\u00b1\u200913.9 years, 54.6% anti\u2010Scl70 positive). The prescription of MMF was more common in men and in anti\u2010Scl70 positive, anticentromere negative patients with interstitial lung disease, myositis, and without a history of digital ulcers. After matching 107 patients with MMF\u2010untreated controls, the overall incidence of vasoactive\/vasodilator treatment escalation events related to digital ulcers over a median follow\u2010up of 40.5 months (interquartile range 23.3\u201360.0) was 0.3 per 100 patient\u2010years in the MMF\u2010treated group and 5.4 per 100 patient\u2010years in the matched control group, with a significant difference in treatment escalation\u2010free survival between the two groups (hazard ratio 0.05, 95% confidence interval 0.01\u20130.38;\n                      <jats:italic>P<\/jats:italic>\n                      value\u00a0=\u00a00.004).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In patients with lcSSc, 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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acr.70039","type":"journal-article","created":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T07:59:45Z","timestamp":1767081585000},"page":"1130-1139","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mycophenolate Mofetil Treatment Reduces the Risk of Treatment Escalation Due to Vascular Complications in Limited Cutaneous Systemic Sclerosis: Emulation of a Target Trial From the Italian Rheumatology Society\n                    <scp>SPRING<\/scp>\n                    Registry"],"prefix":"10.1002","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9819-105X","authenticated-orcid":false,"given":"Enrico","family":"De Lorenzis","sequence":"first","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology Fondazione Policlinico Universitario A. Gemelli IRCCS  Rome Italy"},{"name":"Rheumatology, Faculty of Medicine and Surgery Catholic University of the Sacred Heart  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerlando","family":"Natalello","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology Fondazione Policlinico Universitario A. Gemelli IRCCS  Rome Italy"},{"name":"Rheumatology, Faculty of Medicine and Surgery Catholic University of the Sacred Heart  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5169-3511","authenticated-orcid":false,"given":"Rossella","family":"De Angelis","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, Department of Clinical and Molecular Sciences Polytechnic University of Marche  Ancona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucrezia","family":"Verardi","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology Fondazione Policlinico Universitario A. Gemelli IRCCS  Rome Italy"},{"name":"Rheumatology, Faculty of Medicine and Surgery Catholic University of the Sacred Heart  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0041-3695","authenticated-orcid":false,"given":"Dilia","family":"Giuggioli","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences for Children and Adults University Hospital of Modena and Reggio Emilia School of Medicine  Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluigi","family":"Bajocchi","sequence":"additional","affiliation":[{"name":"Rheumatology Unit Azienda USL IRCCS di Reggio Emilia  Reggio Emilia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Dagna","sequence":"additional","affiliation":[{"name":"Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Scientific Institute Vita\u2010Salute San Raffaele University  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Bellando\u2010Randone","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Scleroderma Unit, Department of Experimental and Clinical Medicine, AOU Careggi University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Zanframundo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Therapeutics Universit\u00e0 di Pavia  Pavia Italy"},{"name":"Division of Rheumatology Fondazione IRCCS Policlinico San Matteo  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosario","family":"Foti","sequence":"additional","affiliation":[{"name":"Rheumatology Unit AOU Policlinico S. Marco  Catania Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7479-4462","authenticated-orcid":false,"given":"Fabio","family":"Cacciapaglia","sequence":"additional","affiliation":[{"name":"Rheumatology Service \u201cF. Miulli\u201d General Hospital Acquaviva delle Fonti \u2010 Department of Medicine and Surgery LUM University \u201cGiuseppe De Gennaro\u201d Casamassima  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Cuomo","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine University of Campania Luigi Vanvitelli  Caserta Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1428-6102","authenticated-orcid":false,"given":"Alarico","family":"Ariani","sequence":"additional","affiliation":[{"name":"Department of Medicine, Internal Medicine and Rheumatology Azienda Ospedaliero Universitaria di Parma  Parma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7417-8093","authenticated-orcid":false,"given":"Edoardo","family":"Rosato","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine Sapienza University of Rome  Roma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4141-6937","authenticated-orcid":false,"given":"Gemma","family":"Lepri","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Scleroderma Unit, Department of Experimental and Clinical Medicine, AOU Careggi University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Girelli","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, AUSL Romagna Ospedale G.B. 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