Treatment of scleroderma-interstitial lung disease with cyclophosphamide is associated with less progressive fibrosis on serial thoracic high-resolution CT scan than placebo: findings from the scleroderma lung study

Abstract

Background: The Scleroderma Lung Study (SLS) demonstrated significant treatment-associated improvements in pulmonary function and symptoms when patients with scleroderma-related interstitial lung disease (SSc-ILD) were treated with a 1-year course of cyclophosphamide (CYC) in a randomized, double-blinded, placebo-controlled clinical trial. This study examined thoracic high-resolution CT (HRCT) scans obtained during the SLS for treatment-associated changes over time.

Methods: Ninety-eight of the 158 subjects (CYC group, 49 subjects; placebo group, 49 subjects) participating in the SLS underwent thoracic HRCT scans both at baseline and after 12 months of treatment, which were available for analysis. Two independent radiologists visually scored the baseline HRCT scans for the presence of ground-glass opacities (GGOs), fibrosis (FIB), and honeycomb cysts (HCs) on a scale of 0 to 4. The treatment effect at 12 months was assessed by a blinded comparison of baseline and follow-up scans for evidence of stability and improvement (not worse) or deterioration (worse).

Results: At the end of treatment, FIB was significantly worse in the placebo treatment group than in the CYC treatment group (p = 0.014). Furthermore, differences in the 12-month change in FIB between the CYC and placebo groups correlated significantly with other outcome measures, including the 12-month changes in FVC (p < 0.05), total lung capacity (p < 0.05), and dyspnea (p < 0.001) scores. However, no differences were noted between the two groups with respect to changes in either GGOs or HCs.

Conclusions: A 1-year course of treatment of SSc-ILD with CYC was associated with treatment-related changes in FIB scores on HRCT scans, which correlated with other measures of treatment response.

Trial registration: ClinicalTrials.gov Identifier: NCT00004563.

Figure 1

Patients with symptomatic SSc-ILD (n = 158) were eligible and randomized into the SLS to receive a 12-month course of treatment with either CYC or placebo according to a randomized, double-blind, placebo-controlled study design. Of these, 98 patients met the current study criteria by having both paired baseline and 12-month HRCT scans available for analysis and BAL fluid cell counts. Forty-nine patients were randomized to the CYC arm, and 49 patients were randomized to the placebo arm.

Figure 2

Representative paired images from a patient in the placebo arm whose FIB was visually scored as being worse over time (A, baseline; B, 12-month follow-up) and a patient in the CYC arm whose serial scans were scored as not worse (C, baseline; D, 12-month follow-up).