Chest
Original ResearchInterstitial Lung DiseaseTreatment 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
Section snippets
Patient Selection
The SLS was a multicenter, randomized, double-blind comparison of a 1-year course of treatment with CYC (≤ 2 mg/kg/d) vs treatment with placebo in 158 patients with dyspnea with active SSc-ILD as defined by evidence on either a HRCT scan (the presence of any GGO through which lung architecture could be seen) or BAL fluid testing (≥ 3.0% neutrophils, ≥ 2.0% eosinophils, or both).5 Pulmonary function was assessed every 3 months during the first year; the primary end point was FVC percent
Results
Of the 158 patients who were eligible and randomized into the SLS, 98 patients (CYC group, 49 patients; placebo group, 49 patients) who had both baseline and 12-month HRCT scans and had completed a BAL procedure were analyzed (Fig 1). Table 1 shows the mean values (or percentage of patients) for clinically relevant baseline demographics and disease characteristics for these 98 patients as well as their worst recorded scores for HRCT scan measures of FIB, GGO, and HC (ie, the worst score among
Discussion
SSc-ILD is a serious and therapeutically challenging manifestation of systemic sclerosis, scleroderma. Although a number of agents have been evaluated as treatments for SSc-ILD, only oral CYC has been proven to be effective in a randomized controlled study5 demonstrating statistically significant placebo-adjusted improvements in FVC and TLC after 12 months of therapy. A small randomized controlled trial6 using IV CYC showed similar results to those with oral CYC, reinforcing this finding. The
Acknowledgments
Author contributions: Drs. Tashkin, Goldin, Elashoff, Roth, Clements, Furst, and Khanna all contributed to the design, oversight, and conduct of the study and in the writing and editing of the manuscript. Drs. Kim and Yan, and Ms. Vasunilashorn all contributed to the processing and statistical analysis of the imaging data and the correlation of the imaging results with the physiologic and patient-centered outcome variables. Dr. Li contributed substantially to the statistical design and analysis
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2021, Autoimmunity ReviewsCitation Excerpt :We identified 33 publications covering 23 different studies that evaluated cyclophosphamide, with the earliest report on cyclophosphamide published in 1993. Eleven publications were analyses of SLS I, a landmark Phase III study evaluating oral cyclophosphamide versus placebo in patients with SSc and ILD over 1 year [13,47–54]. Cyclophosphamide was either administered as intravenous (IV) pulses (doses most commonly ranging from 0.5–1.0 g/m2 body surface area) or orally (generally 1–2 mg/kg/day).
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2021, Rheumatic Disease Clinics of North AmericaOverview on Radiologic Patterns in Interstitial Lung Disease
2021, Encyclopedia of Respiratory Medicine, Second Edition
Funding/Support: This study was funded by research grants R01 HL072424 (Dr. Golding), 5U01 HL60587 (Dr. Tashkin), 5 P30 CA016042-35 (Dr. Li), P01AT003960 (Dr. Li), and 5U01 HL060606 (Dr. Elashoff) from the National Institutes of Health/National Heart, Lung, and Blood Institute.
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