Drs. Roth and Tseng contributed equally to this work.
Predicting treatment outcomes and responder subsets in scleroderma-related interstitial lung disease†
Article first published online: 31 AUG 2011
Copyright © 2011 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 63, Issue 9, pages 2797–2808, September 2011
How to Cite
Roth, M. D., Tseng, C.-H., Clements, P. J., Furst, D. E., Tashkin, D. P., Goldin, J. G., Khanna, D., Kleerup, E. C., Li, N., Elashoff, D., Elashoff, R. M. and Scleroderma Lung Study Research Group (2011), Predicting treatment outcomes and responder subsets in scleroderma-related interstitial lung disease. Arthritis & Rheumatism, 63: 2797–2808. doi: 10.1002/art.30438
ClinicalTrials.gov identifier: NCT00004563.
- Issue published online: 31 AUG 2011
- Article first published online: 31 AUG 2011
- Accepted manuscript online: 5 MAY 2011 10:32AM EST
- Manuscript Accepted: 28 APR 2011
- Manuscript Received: 8 OCT 2010
- NIH (National Heart, Lung, and Blood Institute). Grant Numbers: R01-HL-089758, R01-HL-089901
- National Institute of Allergy and Infectious Diseases. Grant Number: R01-AR-055075
To identify baseline characteristics of patients with scleroderma-related interstitial lung disease (SSc-ILD) that could serve as predictors of the most favorable response to 12-month treatment with oral cyclophosphamide (CYC).
Regression analyses were retrospectively applied to the Scleroderma Lung Study data in order to identify baseline characteristics that correlated with the absolute change in forced vital capacity (FVC) (% predicted values) and the placebo-adjusted change in % predicted FVC over time (the CYC treatment effect).
Completion of the CYC arm of the Scleroderma Lung Study was associated with a placebo-adjusted improvement in the % predicted FVC of 2.11% at 12 months, which increased to 4.16% when patients were followed up for another 6 months (P = 0.014). Multivariate regression analyses identified the maximal severity of reticular infiltrates (assessed as maximum fibrosis scores) on high-resolution computed tomography (HRCT) at baseline, the modified Rodnan skin thickness score (MRSS) at baseline, and the Mahler baseline dyspnea index as independent correlates of treatment response. When patients were stratified on the basis of whether 50% or more of any lung zone was involved by reticular infiltrates on HRCT and/or whether patients exhibited an MRSS of at least 23, a subgroup of patients emerged in whom there was an average CYC treatment effect of 9.81% at 18 months (P < 0.001). Conversely, there was no treatment effect (a −0.58% difference) in patients with less severe HRCT findings and a lower MRSS at baseline.
A retrospective analysis of the Scleroderma Lung Study data identified the severity of reticular infiltrates on baseline HRCT and the baseline MRSS as patient features that might be predictive of responsiveness to CYC therapy.