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.

Copyright © 2011 by the American College of Rheumatology.

Figures

Figure 1. Decline in FVC% predicted, by disease duration

Panel A shows the decline in % FVC over a period of 12 months. Panel B shows the rate of decline in FVC % predicted, adjusted for the baseline FVC % predicted. Numbers above the X-axis represent numbers of subjects corresponding to the data points at the corresponding months. P=NS

Figure 2. FVC% by baseline HRCT-maximum fibrosis score

Panel A shows the decline in % FVC, stratified by maximum HRCT fibrosis at baseline. Panel B shows the rate of decline in FVC % predicted adjusted for the baseline FVC % predicted. Numbers above the X-axis represent numbers of subjects corresponding to the data points. P=0.008

Figure 3. DLCO% by baseline HRCT-maximum fibrosis score

Panel A shows the decline in % DLCO, stratified by maximum HRCT fibrosis at baseline. Panel B shows the rate of decline in DLCO % predicted adjusted for the baseline DLCO % predicted. Numbers above the X-axis represent numbers of subjects corresponding to the data points. P=NS

Figure 4. FVC% by Baseline Maximum HRCT-Fibrosis, by disease duration

Figure shows the rate of decline in FVC % predicted, adjusted for the baseline FVC % predicted for Groups A, B, and C. Numbers above the X-axis represent numbers of subjects corresponding to the data points at the corresponding months. P=0.03 for 0–2 years, NS for 2–4 years, & NS for > 4 years.