Clinical course of lung physiology in patients with scleroderma and interstitial lung disease: Analysis of the Scleroderma Lung Study Placebo Group

Abstract

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.