Expert Perspectives: Defining and managing progressive pulmonary fibrosis in systemic sclerosis

Systemic sclerosis–associated interstitial lung disease (SSc-ILD) is one of the leading causes of morbidity and mortality in SSc, affecting up to three-quarters of patients. The disease course is highly heterogeneous, ranging from indolent, nonprogressive forms to rapidly progressive pulmonary fibrosis (PPF). Identifying patients at risk for progression remains a key clinical challenge. Routine screening with high-resolution computed tomography at diagnosis and regular pulmonary function test monitoring are essential for early detection and timely management. Recent efforts have sought to harmonize the definition of PPF across fibrosing ILDs, recognizing shared clinical and pathophysiological mechanisms beyond idiopathic pulmonary fibrosis. Approximately 20% to 30% of patients with SSc-ILD develop PPF, yet reliable predictors of progression remain elusive. Advances in imaging, functional assessment, and molecular biomarkers hold promise for improving risk stratification. Therapeutic approaches have evolved from conventional immunosuppression toward combination and antifibrotic strategies. Mycophenolate mofetil remains the preferred first-line therapy, whereas nintedanib is the only antifibrotic agent approved for both SSc-ILD and PPF, having demonstrated efficacy in slowing lung function decline. Combination therapy, particularly mycophenolate mofetil with nintedanib or biologics such as rituximab and tocilizumab, is gaining traction in clinical practice despite limited comparative data. Emerging antifibrotic and anti-inflammatory agents offer new therapeutic prospects. This review summarizes current understanding of PPF in SSc-ILD, focusing on its evolving definition, prognostic determinants, and treatment landscape, and highlights unmet needs for personalized, evidence-based management. (Figure presented.).