TY - JOUR
T1 - Cyclophosphamide versus placebo in scleroderma lung disease
AU - Tashkin, Donald P.
AU - Elashoff, Robert
AU - Clements, Philip J.
AU - Goldin, Jonathan
AU - Roth, Michael D.
AU - Furst, Daniel E.
AU - Arriola, Edgar
AU - Silver, Richard
AU - Strange, Charlie
AU - Bolster, Marcy
AU - Seibold, James R.
AU - Riley, David J.
AU - Hsu, Vivien M.
AU - Varga, John
AU - Schraufnagel, Dean E.
AU - Theodore, Arthur
AU - Simms, Robert
AU - Wise, Robert
AU - Wigley, Fredrick
AU - White, Barbara
AU - Steen, Virginia
AU - Read, Charles
AU - Mayes, Maureen
AU - Parsley, Ed
AU - Mubarak, Kamal
AU - Connolly, M. Kari
AU - Golden, Jeffrey
AU - Olman, Mitchell
AU - Fessler, Barri
AU - Rothfield, Naomi
AU - Metersky, Mark
PY - 2006/6/22
Y1 - 2006/6/22
N2 - 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<0.03). There were also treatment-related differences in physiological and symptom outcomes, and the difference in FVC was maintained at 24 months. There was a greater frequency of adverse events in the cyclophosphamide group, but the difference between the two groups in the number of serious adverse events was not significant. CONCLUSIONS: One year of oral cyclophosphamide in patients with symptomatic sclerodermarelated interstitial lung disease had a significant but modest beneficial effect on lung function, dyspnea, thickening of the skin, and the health-related quality of life. The effects on lung function were maintained through the 24 months of the study.
AB - 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<0.03). There were also treatment-related differences in physiological and symptom outcomes, and the difference in FVC was maintained at 24 months. There was a greater frequency of adverse events in the cyclophosphamide group, but the difference between the two groups in the number of serious adverse events was not significant. CONCLUSIONS: One year of oral cyclophosphamide in patients with symptomatic sclerodermarelated interstitial lung disease had a significant but modest beneficial effect on lung function, dyspnea, thickening of the skin, and the health-related quality of life. The effects on lung function were maintained through the 24 months of the study.
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U2 - 10.1056/NEJMoa055120
DO - 10.1056/NEJMoa055120
M3 - Article
C2 - 16790698
AN - SCOPUS:33745227399
SN - 0028-4793
VL - 354
SP - 2655
EP - 2666
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 25
ER -