Treatment of systemic sclerosis-associated interstitial lung disease: a work in progress

In 2014, two randomised controlled trials were published showing that nintedanib and pirfenidone can slow lung function decline in patients with idiopathic pulmonary fibrosis, 1 King Jr, TE Bradford WZ Castro-Bernardini S et al. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014; 370: 2083-2092 Crossref PubMed Scopus (2085) Google Scholar , 2 Richeldi L du Bois RM Raghu G et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014; 370: 2071-2082 Crossref PubMed Scopus (2302) Google Scholar prompting an era of antifibrotic therapy for this devastating disease. Overlapping features between idiopathic pulmonary fibrosis and other fibrosing interstitial lung diseases (ILDs) naturally led clinicians to wonder whether antifibrotic therapy could effectively treat a broad range of conditions that result in pulmonary fibrosis. The Safety and Efficacy of Nintedanib in Systemic Sclerosis (SENSCIS) trial suggested as much after nintedanib effectively slowed the decline in lung function in patients with systemic sclerosis-associated ILD (SSc-ILD). 3 Distler O Gahlemann M Maher TM Nintedanib for systemic sclerosis-associated interstitial lung disease. Reply. N Engl J Med. 2019; 381: 1596-1597 PubMed Google Scholar Despite a relatively small treatment effect compared with that reported in studies of idiopathic pulmonary fibrosis, 1 King Jr, TE Bradford WZ Castro-Bernardini S et al. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014; 370: 2083-2092 Crossref PubMed Scopus (2085) Google Scholar , 2 Richeldi L du Bois RM Raghu G et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014; 370: 2071-2082 Crossref PubMed Scopus (2302) Google Scholar nintedanib was approved for the treatment of SSc-ILD in several countries throughout Asia, North America, and Europe. Efficacy and safety of nintedanib in patients with systemic sclerosis-associated interstitial lung disease treated with mycophenolate: a subgroup analysis of the SENSCIS trialNintedanib reduced the progression of interstitial lung disease both in patients with SSc-ILD who were and were not using mycophenolate at baseline, with no heterogeneity in its treatment effect detected between the subgroups. The adverse event profile of nintedanib was similar in the subgroups by mycophenolate use. Our findings suggest that the combination of mycophenolate and nintedanib offers a safe treatment option for patients with SSc-ILD. More data are needed on the benefits of initial combination therapy versus a sequential approach to treatment of SSc-ILD. Full-Text PDF