Nintedanib—A Potential New Therapy for Systemic Sclerosis-associated Interstitial Lung Disease

Abstract

Systemic sclerosis (SSc) is an autoimmune disorder characterized by inflammation and fibrosis of the skin and other internal organs, especially the lungs. SSc-associated interstitial lung disease (SSc-ILD) is the most common complication of SSc and leading cause of morbidity and mortality in these patients. As such, there is a significant unmet need for earlier, more accurate diagnosis and implementation of safe, more effective therapies. The pathogenesis of SSc-ILD is a complex process that involves cellular and humoral immune dysregulation, inflammatory mediators, and vascular and fibrotic mechanisms. Traditional therapeutic strategies have focused on reducing chronic inflammation and the immunomodulation. Mycophenolate mofetil is currently considered the first-line therapy for SSc-ILD based on the Scleroderma Lung Study (SLS-II), which showed equivalent efficacy with fewer adverse events compared with cyclophosphamide. Nintedanib is an intracellular tyrosine kinase inhibitor with antifibrotic, anti-inflammatory, and vascular remodeling effects. Currently approved for idiopathic pulmonary fibrosis, nintedanib was recently evaluated for safety and efficacy in SSc-ILD. Based upon the results of this pivotal trial, nintedanib is the first ever treatment approved by the US Food and Drug Administration for SSc-ILD. This review focuses on the pathogenesis of SSc-ILD and the role of nintedanib in the treatment algorithm for these patients.