BACKGROUND: Interstitial lung disease (ILD) is a common manifestation of 
systemic sclerosis and a leading cause of systemic sclerosis-related death. 
Nintedanib, a tyrosine kinase inhibitor, has been shown to have antifibrotic and 
antiinflammatory effects in preclinical models of systemic sclerosis and ILD.
METHODS: We conducted a randomized, double-blind, placebo-controlled trial to 
investigate the efficacy and safety of nintedanib in patients with ILD 
associated with systemic sclerosis. Patients who had systemic sclerosis with an 
onset of the first non-Raynaud's symptom within the past 7 years and a 
high-resolution computed tomographic scan that showed fibrosis affecting at 
least 10% of the lungs were randomly assigned, in a 1:1 ratio, to receive 150 mg 
of nintedanib, administered orally twice daily, or placebo. The primary end 
point was the annual rate of decline in forced vital capacity (FVC), assessed 
over a 52-week period. Key secondary end points were absolute changes from 
baseline in the modified Rodnan skin score and in the total score on the St. 
George's Respiratory Questionnaire (SGRQ) at week 52.
RESULTS: A total of 576 patients received at least one dose of nintedanib or 
placebo; 51.9% had diffuse cutaneous systemic sclerosis, and 48.4% were 
receiving mycophenolate at baseline. In the primary end-point analysis, the 
adjusted annual rate of change in FVC was -52.4 ml per year in the nintedanib 
group and -93.3 ml per year in the placebo group (difference, 41.0 ml per year; 
95% confidence interval [CI], 2.9 to 79.0; P = 0.04). Sensitivity analyses based 
on multiple imputation for missing data yielded P values for the primary end 
point ranging from 0.06 to 0.10. The change from baseline in the modified Rodnan 
skin score and the total score on the SGRQ at week 52 did not differ 
significantly between the trial groups, with differences of -0.21 (95% CI, -0.94 
to 0.53; P = 0.58) and 1.69 (95% CI, -0.73 to 4.12 [not adjusted for multiple 
comparisons]), respectively. Diarrhea, the most common adverse event, was 
reported in 75.7% of the patients in the nintedanib group and in 31.6% of those 
in the placebo group.
CONCLUSIONS: Among patients with ILD associated with systemic sclerosis, the 
annual rate of decline in FVC was lower with nintedanib than with placebo; no 
clinical benefit of nintedanib was observed for other manifestations of systemic 
sclerosis. The adverse-event profile of nintedanib observed in this trial was 
similar to that observed in patients with idiopathic pulmonary fibrosis; 
gastrointestinal adverse events, including diarrhea, were more common with 
nintedanib than with placebo. (Funded by Boehringer Ingelheim; SENSCIS 
ClinicalTrials.gov number, NCT02597933.).