Relevance of immunomodulatory therapy for interstitial lung disease in systemic sclerosis

Systemic sclerosis is an autoimmune disease that prominently leads to skin and tissue fibrosis. The efficacy of autologous stem cell transplantation not only attests to the autoimmune pathophysiology for systemic sclerosis, but also for interstitial lung disease as its most frequent manifestation of fatal organ involvement. Accordingly, a variety of immunomodulatory therapies were tried on patients with systemic sclerosis-interstitial lung disease. Until very recently, all of these therapeutic approaches constituted off-label treatment for systemic sclerosis, given that neither of these therapies was approved by the United States Food and Drug Administration (FDA) or the European Medicines Agency. For tocilizumab, this has now changed with FDA approval in March 2021. Already 2020, nintedanib, which is an antifibrotic drug that does not target autoimmunity, became the first approved drug for interstitial lung disease in systemic sclerosis. The present review analyzes the evidence for immunomodulatory treatment of systemic sclerosis-associated interstitial lung disease. The review focuses on randomized controlled trials, which provides evidence for the effects of drugs such as cyclophosphamide, mycophenolate, rituximab and tocilizumab.