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 high-resolution computed tomography, or both. Patients received oral cyclophosphamide (< or =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 scleroderma-related 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. Copyright 2006 Massachusetts Medical Society.
RCT Entities:
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 high-resolution computed tomography, or both. Patients received oral cyclophosphamide (< or =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 scleroderma-related 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. Copyright 2006 Massachusetts Medical Society.
Authors: Elizabeth Schulman; Kun Chen; Gregory Saboeiro; Abraham Sanders; Kyriakos Kirou; Robert F Spiera; Anne R Bass; Doruk Erkan Journal: HSS J Date: 2010-10-26
Authors: P A Merkel; N P Silliman; P J Clements; C P Denton; D E Furst; M D Mayes; J E Pope; R P Polisson; J B Streisand; J R Seibold Journal: Arthritis Rheum Date: 2012-10
Authors: Dinesh Khanna; Daniel E Furst; Philip J Clements; Yannick Allanore; Murray Baron; Lazlo Czirjak; Oliver Distler; Ivan Foeldvari; Masataka Kuwana; Marco Matucci-Cerinic; Maureen Mayes; Thomas Medsger; Peter A Merkel; Janet E Pope; James R Seibold; Virginia Steen; Wendy Stevens; Christopher P Denton Journal: J Scleroderma Relat Disord Date: 2017 Jan-Apr
Authors: Donald P Tashkin; Robert Elashoff; Philip J Clements; Michael D Roth; Daniel E Furst; Richard M Silver; Jonathan Goldin; Edgar Arriola; Charlie Strange; Marcy B Bolster; James R Seibold; David J Riley; Vivien M Hsu; John Varga; Dean Schraufnagel; Arthur Theodore; Robert Simms; Robert Wise; Fred Wigley; Barbara White; Virginia Steen; Charles Read; Maureen Mayes; Ed Parsley; Kamal Mubarak; M Kari Connolly; Jeffrey Golden; Mitchell Olman; Barri Fessler; Naomi Rothfield; Mark Metersky; Dinesh Khanna; Ning Li; Gang Li Journal: Am J Respir Crit Care Med Date: 2007-08-23 Impact factor: 21.405