Effects of 1-year treatment with cyclophosphamide on outcomes at 2 years in scleroderma lung disease

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 A Wise, Fredrick Wigley, Barbara White & 14 others 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

Research output: Contribution to journalArticle

Abstract

Rationale: The Scleroderma Lung Study enrolled 158 patients with scleroderma-related interstitial lung disease in a placebo-controlled trial of oral cyclophosphamide (CYC). Although treatment-related benefits in pulmonary function, skin scores, and patient-centered outcomes were demonstrated after 1 year of therapy, the duration of benefit beyond 1 year was unclear. Objectives: A second year of follow-up was performed to determine if these effects persisted after stopping treatment. Methods: A detailed analysis of data obtained over the two years of the study was performed. Measurements and Main Results: Using a longitudinal joint model, we analyzed FVC, 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 nonignorable missing data. Evaluable subjects (72 CYC; 73 placebo) included 93 who completed all visits plus 52 who completed at least 6 months of therapy and returned at 24 month or had their 24-month data imputed. The beneficial effects of CYC on pulmonary function and health status continued to increase through 18 months, after which they dissipated, whereas skin improvements dissipated after 12 months. In contrast, the positive effect on dyspnea persisted through 24 months. Adverse events were uncommon. Conclusions: One year of CYC 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 CYC should be considered.

Original languageEnglish (US)
Pages (from-to)1026-1034
Number of pages9
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume176
Issue number10
DOIs
StatePublished - Nov 15 2007

Fingerprint

Cyclophosphamide
Lung Diseases
Dyspnea
Lung
Skin
Health Status
Therapeutics
Placebos
Total Lung Capacity
Interstitial Lung Diseases
Therapeutic Uses
Fibrosis
Joints
Health

Keywords

  • Cyclophosphamide
  • Interstitial lung disease
  • Scleroderma
  • Systemic sclerosis

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Effects of 1-year treatment with cyclophosphamide on outcomes at 2 years in scleroderma lung disease. / Tashkin, Donald P.; Elashoff, Robert; Clements, Philip J.; Roth, Michael D.; Furst, Daniel E.; Silver, Richard M.; Goldin, Jonathan; Arriola, Edgar; Strange, Charlie; Bolster, Marcy B.; Seibold, James R.; Riley, David J.; Hsu, Vivien M.; Varga, John; Schraufnagel, Dean; Theodore, Arthur; Simms, Robert; Wise, Robert A; Wigley, Fredrick; White, Barbara; Steen, Virginia; Read, Charles; Mayes, Maureen; Parsley, Ed; Mubarak, Kamal; Connolly, M. Kari; Golden, Jeffrey; Olman, Mitchell; Fessler, Barri; Rothfield, Naomi; Metersky, Mark; Khanna, Dinesh; Li, Ning; Li, Gang.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 176, No. 10, 15.11.2007, p. 1026-1034.

Research output: Contribution to journalArticle

Tashkin, DP, Elashoff, R, Clements, PJ, Roth, MD, Furst, DE, Silver, RM, Goldin, J, Arriola, E, Strange, C, Bolster, MB, Seibold, JR, Riley, DJ, Hsu, VM, Varga, J, Schraufnagel, D, Theodore, A, Simms, R, Wise, RA, Wigley, F, White, B, Steen, V, Read, C, Mayes, M, Parsley, E, Mubarak, K, Connolly, MK, Golden, J, Olman, M, Fessler, B, Rothfield, N, Metersky, M, Khanna, D, Li, N & Li, G 2007, 'Effects of 1-year treatment with cyclophosphamide on outcomes at 2 years in scleroderma lung disease', American Journal of Respiratory and Critical Care Medicine, vol. 176, no. 10, pp. 1026-1034. https://doi.org/10.1164/rccm.200702-326OC
Tashkin, Donald P. ; Elashoff, Robert ; Clements, Philip J. ; Roth, Michael D. ; Furst, Daniel E. ; Silver, Richard M. ; Goldin, Jonathan ; Arriola, Edgar ; Strange, Charlie ; Bolster, Marcy B. ; Seibold, James R. ; Riley, David J. ; Hsu, Vivien M. ; Varga, John ; Schraufnagel, Dean ; Theodore, Arthur ; Simms, Robert ; Wise, Robert A ; Wigley, Fredrick ; White, Barbara ; Steen, Virginia ; Read, Charles ; Mayes, Maureen ; Parsley, Ed ; Mubarak, Kamal ; Connolly, M. Kari ; Golden, Jeffrey ; Olman, Mitchell ; Fessler, Barri ; Rothfield, Naomi ; Metersky, Mark ; Khanna, Dinesh ; Li, Ning ; Li, Gang. / Effects of 1-year treatment with cyclophosphamide on outcomes at 2 years in scleroderma lung disease. In: American Journal of Respiratory and Critical Care Medicine. 2007 ; Vol. 176, No. 10. pp. 1026-1034.
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abstract = "Rationale: The Scleroderma Lung Study enrolled 158 patients with scleroderma-related interstitial lung disease in a placebo-controlled trial of oral cyclophosphamide (CYC). Although treatment-related benefits in pulmonary function, skin scores, and patient-centered outcomes were demonstrated after 1 year of therapy, the duration of benefit beyond 1 year was unclear. Objectives: A second year of follow-up was performed to determine if these effects persisted after stopping treatment. Methods: A detailed analysis of data obtained over the two years of the study was performed. Measurements and Main Results: Using a longitudinal joint model, we analyzed FVC, 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 nonignorable missing data. Evaluable subjects (72 CYC; 73 placebo) included 93 who completed all visits plus 52 who completed at least 6 months of therapy and returned at 24 month or had their 24-month data imputed. The beneficial effects of CYC on pulmonary function and health status continued to increase through 18 months, after which they dissipated, whereas skin improvements dissipated after 12 months. In contrast, the positive effect on dyspnea persisted through 24 months. Adverse events were uncommon. Conclusions: One year of CYC 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 CYC should be considered.",
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AU - Tashkin, Donald P.

AU - Elashoff, Robert

AU - Clements, Philip J.

AU - Roth, Michael D.

AU - Furst, Daniel E.

AU - Silver, Richard M.

AU - Goldin, Jonathan

AU - Arriola, Edgar

AU - Strange, Charlie

AU - Bolster, Marcy B.

AU - Seibold, James R.

AU - Riley, David J.

AU - Hsu, Vivien M.

AU - Varga, John

AU - Schraufnagel, Dean

AU - Theodore, Arthur

AU - Simms, Robert

AU - Wise, Robert A

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

AU - Khanna, Dinesh

AU - Li, Ning

AU - Li, Gang

PY - 2007/11/15

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N2 - Rationale: The Scleroderma Lung Study enrolled 158 patients with scleroderma-related interstitial lung disease in a placebo-controlled trial of oral cyclophosphamide (CYC). Although treatment-related benefits in pulmonary function, skin scores, and patient-centered outcomes were demonstrated after 1 year of therapy, the duration of benefit beyond 1 year was unclear. Objectives: A second year of follow-up was performed to determine if these effects persisted after stopping treatment. Methods: A detailed analysis of data obtained over the two years of the study was performed. Measurements and Main Results: Using a longitudinal joint model, we analyzed FVC, 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 nonignorable missing data. Evaluable subjects (72 CYC; 73 placebo) included 93 who completed all visits plus 52 who completed at least 6 months of therapy and returned at 24 month or had their 24-month data imputed. The beneficial effects of CYC on pulmonary function and health status continued to increase through 18 months, after which they dissipated, whereas skin improvements dissipated after 12 months. In contrast, the positive effect on dyspnea persisted through 24 months. Adverse events were uncommon. Conclusions: One year of CYC 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 CYC should be considered.

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