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 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.
Tashkin
Donald P
DP
University of California at Los Angeles, Los Angeles, USA. dtashkin@mednet.ucla.edu
Elashoff
Robert
R
Clements
Philip J
PJ
Goldin
Jonathan
J
Roth
Michael D
MD
Furst
Daniel E
DE
Arriola
Edgar
E
Silver
Richard
R
Strange
Charlie
C
Bolster
Marcy
M
Seibold
James R
JR
Riley
David J
DJ
Hsu
Vivien M
VM
Varga
John
J
Schraufnagel
Dean E
DE
Theodore
Arthur
A
Simms
Robert
R
Wise
Robert
R
Wigley
Fredrick
F
White
Barbara
B
Steen
Virginia
V
Read
Charles
C
Mayes
Maureen
M
Parsley
Ed
E
Mubarak
Kamal
K
Connolly
M Kari
MK
Golden
Jeffrey
J
Olman
Mitchell
M
Fessler
Barri
B
Rothfield
Naomi
N
Metersky
Mark
M
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001327:Autoimmune Diseases / Q000188:drug therapy*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007970:Leukopenia / Q000139:chemically induced; D017563:Lung Diseases, Interstitial / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D012129:Respiratory Function Tests; D012595:Scleroderma, Systemic / Q000188:drug therapy* / Q000276:immunology; D016896:Treatment Outcome; D014797:Vital Capacity / Q000187:drug effects
D007166:Immunosuppressive Agents; D003520:Cyclophosphamide