A Narrative Review of Therapeutic Options in Systemic Sclerosis Associated Interstitial Lung Disease

Abstract

Background: Interstitial lung disease (ILD) has replaced scleroderma renal crisis as the leading cause of mortality in systemic sclerosis (SSc), with a 10-year mortality of 40%. There have been well-powered randomised control trials (RCTs) demonstrating the effect of cyclophosphamide (CYC), mycophenolic acid (MMF), nintedanib and tocilizumab (TCZ) in SSc-ILD but a paucity of sufficiently powered studies investigating other agents in the disease. Methods: This is a narrative review which examines the existing evidence for immunosuppressive treatments, transplant and adjunctive therapies in SSc-ILD by reviewing the key landmark trials in the last two decades. Results: MMF for 2 years is as effective as oral CYC for 1 year. Rituximab (RTX) is non-inferior to CYC. TCZ appears to have a beneficial effective regardless of the extent of lung involvement. Conclusions: There is now a strong evidence base supporting the use of MMF as the first line option in SSc-ILD. RTX, CYC and TCZ are viable therapeutic options if there is ILD progression on MMF. Anti-fibrotic and pulmonary arterial (PAH) treatments likely add long-term synergistic benefits. There remains a role for lung transplantation in select patients.