Published ahead of print on August 23, 2007, doi:10.1164/rccm.200702-326OC
Am. J. Respir. Crit. Care Med., Volume 176, Number 10, November 2007, 1026-1034
A more recent version of this article appeared on November 15, 2007
Submitted on February 26, 2007
Accepted on August 23, 2007
Effects of 1-year Treatment with Cyclophosphamide on Outcomes at 2 Years in Scleroderma Lung Disease
Donald P Tashkin1*, Robert Elashoff2, Philip J Clements1, Michael D Roth1, Daniel E Furst1, Richard M Silver3, Jonathan Goldin4, Edgar Arriola5, Charlie Strange3, Marcy B Bolster2, James R Seibold6, David J Riley6, Vivien M Hsu6, John Varga7, Dean Schraufnagel7, Arthur Theodore8, Robert Simms8, Robert Wise9, Fred Wigley9, and Scleroderma Lung Study Research Group10
1 Department of Medicine, University of California Los Angeles, David Geffen School of Medicine, Los Angeles, CA, United States,
2 Department of Biomathematics, University of California Los Angeles, David Geffen School of Medicine, Los Angeles, CA, USA,
3 Department of Medicine, Medical University of South Carolina, Charleston, SC, USA,
4 Department of Radiological Sciences, University of California Los Angeles, David Geffen School of Medicine, Los Angeles, CA, USA,
5 UCLA Medical Center, Pharmaceutical Services, Los Angeles, CA, USA,
6 Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ, USA,
7 Department of Medicine, University of Illinois Chicago, Chicago, IL, USA,
8 Department of Medicine, Boston University, Boston, MA, USA,
9 Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA,
10 Department of Medicine, Georgetown University, Washington DC, DC, USA; Department of Medicine, University of Texas Houston Medical School, Houston, TX, USA; Department of Medicine, Wayne State University, Detroit, MI, USA
* To whom correspondence should be addressed. E-mail: dtashkin{at}mednet.ucla.edu.
Rationale: The Scleroderma Lung Study enrolled 158 patients with scleroderma-related interstitial lung disease into a placebo-controlled trial of oral cyclophosphamide. While treatment-related benefits in pulmonary function, skin scores and patient-centered outcomes were demonstrated after one year of therapy, the duration of benefit beyond one year was unclear.
Objectives: A second year of follow-up was performed to determine if these effects persisted after stopping treatment.
Measurements and Main Results: Using a longitudinal joint model, we analyzed forced vital capacity, total lung capacity, transitional dyspnea index, Rodnan skin scores and the Health Assessment Questionnaire-Disability Index during the second year after adjusting for baseline values, baseline fibrosis score and non-ignorable missing data. Evaluable subjects (72 cyclophosphamide; 73 placebo) included 93 who completed all visits plus 52 who completed  6 months of therapy and returned at 24 months or had their 24-month data imputed. The beneficial effects of cyclophosphamide on pulmonary function and health status continued to increase through 18 months, after which they dissipated, while skin improvements dissipated after 12 months. In contrast, the positive effect on dyspnea persisted through 24 months. Adverse events were uncommon.
Conclusion: One year of cyclophosphamide improved lung function, skin scores, dyspnea and health status-disability, effects which either persisted or increased further for several months after stopping therapy. However, except for a sustained impact on dyspnea, all of these effects waned and were no longer apparent at 24 months. Treatment strategies aimed at extending the positive therapeutic effects observed with cyclophosphamide should be considered.
www.clinical trials.gov - identifier NCT00004563
Key words: systemic sclerosis; scleroderma; interstitial lung disease; cyclophosphamide
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Copyright © 2007 American Thoracic Society
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