Clinical Course of Lung Physiology in Patients With Scleroderma and Interstitial Lung Disease Analysis of the Scleroderma Lung Study Placebo Group

Objective. Patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) are thought to have the greatest decline in lung function (forced vital capacity [FVC] % predicted) in the early years after disease onset. The aim of this study was to assess the natural history of the decline in FVC % predicted in patients receiving placebo in the Scleroderma Lung Study and to evaluate possible factors for cohort enrichment in future therapeutic trials. Methods. Patients randomized to receive placebo (n = 79) were divided into 3 groups based on the duration of SSc (0-2 years, 2-4 years, and >4 years). Descriptive statistics and a mixed-effects model were used to analyze the rate of decline in the FVC % predicted over a 1-year period. Additional analyses stratified according to the severity of fibrosis on high-resolution computed tomography (HRCT) were performed, and interactions between disease severity and disease duration were explored. Results. The mean +/- SD decline in the unadjusted FVC % predicted during the 1-year period was 4.2 +/- 12.8%. At baseline, 28.5%, 43.0%, and 28.5% of patients were in the groups with disease durations of 0-2 years, 2-4 years, and > 4 years, respectively. The rate of decline in the FVC % predicted was not significantly different across the 3 disease groups (P=0.85). When stratified by baseline fibrosis on HRCT, the rate of decline in the FVC % predicted was statistically significantly greater in the group with severe fibrosis (mean annualized decline in the FVC % predicted 7.2% versus 2.7% in the groups with no or moderate fibrosis; P=0.008). The decline observed in the group with severe fibrosis was most pronounced in those with a relatively short disease duration (0-2 years; annualized decline 7.0%). Conclusion. Among patients with SSc-ILD in the Scleroderma Lung Study, the rates of progression of lung disease were similar irrespective of disease duration. The baseline HRCT fibrosis score is a predictor of a future decline in the FVC % predicted in the absence of effective treatment.