Cyclophosphamide versus Placebo in Scleroderma Lung Disease

BACKGROUND We conducted a double-blind, randomized, placebo-controlled trial to determine the effects of oral cyclophosphamide on lung function and health-related symptoms in patients with evidence of active alveolitis and scleroderma-related interstitial lung disease. METHODS At 13 clinical centers throughout the United States, we enrolled 158 patients with scleroderma, restrictive lung physiology, dyspnea, and evidence of inflammatory interstitial lung disease on examination of bronchoalveolar-lavage fluid, thoracic highresolution computed tomography, or both. Patients received oral cyclophosphamide (≤2 mg per kilogram of body weight per day) or matching placebo for one year and were followed for an additional year. Pulmonary function was assessed every three months during the first year, and the primary end point was the forced vital capacity (FVC, expressed as a percentage of the predicted value) at 12 months, after adjustment for the baseline FVC. RESULTS Of 158 patients, 145 completed at least six months of treatment and were included in the analysis. The mean absolute difference in adjusted 12-month FVC percent predicted between the cyclophosphamide and placebo groups was 2.53 percent (95 percent confidence interval, 0.28 to 4.79 percent), favoring cyclophosphamide (P