Advancements in the treatment of interstitial lung disease in systemic sclerosis with the approval of mycophenolate mofetil

Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by widespread fibrosis affecting various organs. This disorder has two main subtypes based on the extent of cutaneous fibrosis (limited and diffuse cutaneous SSc). Interstitial lung disease (ILD) occurs in approximately 50% and 25% of patients with diffuse cutaneous SSc and limited cutaneous SSc, respectively. In Japan, over 10,000 people are estimated to have ILD. Out of 10,000 SSc-ILD, at least 4000 patients may have slowly progressive ILD which leads to respiratory failure. Treatment of ILD in patients with SSc includes immunosuppressive and anti-fibrotic agents. Mycophenolate mofetil (MMF) is strongly recommended as a first-line immunosuppressive agent for the treatment of SSc-ILD according to recent American Thoracic Society clinical practice guidelines. However, as of February 2024, MMF was only approved in Japan for patients with organ transplants or lupus nephritis through health insurance policies. Cyclophosphamide is an alternative initial immunomodulatory agent for patients with the disease because it has an efficacy comparable to that of MMF. However, this agent had significantly higher toxicity than MMF. For patients with progressive pulmonary fibrosis, despite the use of immunosuppressive agents, adding nintedanib or rituximab to MMF or cyclophosphamide is recommended. This review explores the treatment of ILD associated with SSc in Japan with the approval of MMF based on the latest American Thoracic Society guideline.