Managing Systemic Sclerosis-Related Interstitial Lung Disease in the Modern Treatment Era

Interstitial lung disease (ILD) affects the majority of patients with systemic sclerosis (SSc) and is the leading cause of death in SSc. Traditionally, treatments for SSc-ILD have targeted broad suppression of the immune system with agents such as cyclophosphamide and mycophenolate. The recently published Scleroderma Lung Study (SLS) II demonstrated that treatment with either oral cyclophosphamide or mycophenolate led to similar improvement in lung function, dyspnea and radiographic extent of fibrosis. However, with the emergence of anti-fibrotic therapy for the treatment of idiopathic pulmonary fibrosis, the repurposing of biologic agents used to treat other connective tissue diseases, and the introduction of hematopoetic stem-cell transplantation for patients with early diffuse SSc, options for managing SSc-ILD have increased. For the first time ever, patients and physicians have choices for how to treat SSc-ILD. At the same time, the study and administration of these novel therapeutic agents have raised important clinical research questions that warrant further investigation. This review describes the current and experimental therapies available for SSc-ILD. This review also explores unanswered questions directly relevant to patient care and future research efforts in this area, including questions on indications for initiation of SSc-ILD therapy, the use of maintenance SSc-ILD therapy and the duration of SSc-ILD therapy. Conducting studies designed to answer these important questions is central to advancing SSc-ILD research and improving outcomes for patients with this devastating disease.