A novel therapeutic approach to the treatment of scleroderma-associated pulmonary complications

Safety and efficacy of combination therapy with imatinib and cyclophosphamide

I. Sabnani, M. J. Zucker, Elliot Rosenstein, D. A. Baran, L. H. Arroyo, P. Tsang, M. Zubair, V. Rivera

Research output: Contribution to journalArticle

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Abstract

Objective. Scleroderma-related interstitial lung disease (SSc-ILD) has limited therapeutic options due to unclear pathogenesis. Recently, PDGF receptor (PDGFR) amplification has been postulated to cause fibrosis. We hypothesized that a combination of immunosuppressive agents, e.g. cyclophosphamide (CYC) and imatinib (PDGFR inhibitor), might be useful for treating SSc-related ILD. Our objective was to evaluate the safety and efficacy of this combination therapy in scleroderma-related pulmonary disease. Methods. Five patients with advanced SSc-ILD underwent comprehensive cardiopulmonary evaluation, followed by administration of oral imatinib (200 mg/day) and intravenous CYC (500 mg every 3 weeks). Safety was assessed by close monitoring of complete blood count, liver and cardiac functions. Efficacy was evaluated by measuring pulmonary functions at 6 and 12 months. Results. Of the five patients in the study, four had severe and one had mild restrictive lung disease. All patients tolerated the combination treatment without myelosuppression, deterioration of liver functions or cardiac status. Only one patient had mild fluid overload requiring diuretics. Two patients completed 1 yr of treatment. Only the patient with mild restrictive lung disease showed improvement in pulmonary function. Conclusion. The combination of intravenous CYC and oral imatinib was well-tolerated without major side effects. Clinical improvement was seen in only the patient with mild restrictive disease. To our knowledge, this is the first study examining the safety, tolerability and efficacy of imatinib in combination with CYC in scleroderma-related pulmonary disease. Large prospective trials are needed to further determine optimal timing, dose and duration of this regimen.

Original languageEnglish (US)
Pages (from-to)49-52
Number of pages4
JournalRheumatology
Volume48
Issue number1
DOIs
StatePublished - Jan 1 2009

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Cyclophosphamide
Safety
Lung
Lung Diseases
Platelet-Derived Growth Factor Receptors
Therapeutics
Blood Cell Count
Liver
Interstitial Lung Diseases
Immunosuppressive Agents
Imatinib Mesylate
Diuretics
Oral Administration
Fibrosis

All Science Journal Classification (ASJC) codes

  • Rheumatology
  • Pharmacology (medical)

Cite this

Sabnani, I. ; Zucker, M. J. ; Rosenstein, Elliot ; Baran, D. A. ; Arroyo, L. H. ; Tsang, P. ; Zubair, M. ; Rivera, V. / A novel therapeutic approach to the treatment of scleroderma-associated pulmonary complications : Safety and efficacy of combination therapy with imatinib and cyclophosphamide. In: Rheumatology. 2009 ; Vol. 48, No. 1. pp. 49-52.
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abstract = "Objective. Scleroderma-related interstitial lung disease (SSc-ILD) has limited therapeutic options due to unclear pathogenesis. Recently, PDGF receptor (PDGFR) amplification has been postulated to cause fibrosis. We hypothesized that a combination of immunosuppressive agents, e.g. cyclophosphamide (CYC) and imatinib (PDGFR inhibitor), might be useful for treating SSc-related ILD. Our objective was to evaluate the safety and efficacy of this combination therapy in scleroderma-related pulmonary disease. Methods. Five patients with advanced SSc-ILD underwent comprehensive cardiopulmonary evaluation, followed by administration of oral imatinib (200 mg/day) and intravenous CYC (500 mg every 3 weeks). Safety was assessed by close monitoring of complete blood count, liver and cardiac functions. Efficacy was evaluated by measuring pulmonary functions at 6 and 12 months. Results. Of the five patients in the study, four had severe and one had mild restrictive lung disease. All patients tolerated the combination treatment without myelosuppression, deterioration of liver functions or cardiac status. Only one patient had mild fluid overload requiring diuretics. Two patients completed 1 yr of treatment. Only the patient with mild restrictive lung disease showed improvement in pulmonary function. Conclusion. The combination of intravenous CYC and oral imatinib was well-tolerated without major side effects. Clinical improvement was seen in only the patient with mild restrictive disease. To our knowledge, this is the first study examining the safety, tolerability and efficacy of imatinib in combination with CYC in scleroderma-related pulmonary disease. Large prospective trials are needed to further determine optimal timing, dose and duration of this regimen.",
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A novel therapeutic approach to the treatment of scleroderma-associated pulmonary complications : Safety and efficacy of combination therapy with imatinib and cyclophosphamide. / Sabnani, I.; Zucker, M. J.; Rosenstein, Elliot; Baran, D. A.; Arroyo, L. H.; Tsang, P.; Zubair, M.; Rivera, V.

In: Rheumatology, Vol. 48, No. 1, 01.01.2009, p. 49-52.

Research output: Contribution to journalArticle

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T1 - A novel therapeutic approach to the treatment of scleroderma-associated pulmonary complications

T2 - Safety and efficacy of combination therapy with imatinib and cyclophosphamide

AU - Sabnani, I.

AU - Zucker, M. J.

AU - Rosenstein, Elliot

AU - Baran, D. A.

AU - Arroyo, L. H.

AU - Tsang, P.

AU - Zubair, M.

AU - Rivera, V.

PY - 2009/1/1

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N2 - Objective. Scleroderma-related interstitial lung disease (SSc-ILD) has limited therapeutic options due to unclear pathogenesis. Recently, PDGF receptor (PDGFR) amplification has been postulated to cause fibrosis. We hypothesized that a combination of immunosuppressive agents, e.g. cyclophosphamide (CYC) and imatinib (PDGFR inhibitor), might be useful for treating SSc-related ILD. Our objective was to evaluate the safety and efficacy of this combination therapy in scleroderma-related pulmonary disease. Methods. Five patients with advanced SSc-ILD underwent comprehensive cardiopulmonary evaluation, followed by administration of oral imatinib (200 mg/day) and intravenous CYC (500 mg every 3 weeks). Safety was assessed by close monitoring of complete blood count, liver and cardiac functions. Efficacy was evaluated by measuring pulmonary functions at 6 and 12 months. Results. Of the five patients in the study, four had severe and one had mild restrictive lung disease. All patients tolerated the combination treatment without myelosuppression, deterioration of liver functions or cardiac status. Only one patient had mild fluid overload requiring diuretics. Two patients completed 1 yr of treatment. Only the patient with mild restrictive lung disease showed improvement in pulmonary function. Conclusion. The combination of intravenous CYC and oral imatinib was well-tolerated without major side effects. Clinical improvement was seen in only the patient with mild restrictive disease. To our knowledge, this is the first study examining the safety, tolerability and efficacy of imatinib in combination with CYC in scleroderma-related pulmonary disease. Large prospective trials are needed to further determine optimal timing, dose and duration of this regimen.

AB - Objective. Scleroderma-related interstitial lung disease (SSc-ILD) has limited therapeutic options due to unclear pathogenesis. Recently, PDGF receptor (PDGFR) amplification has been postulated to cause fibrosis. We hypothesized that a combination of immunosuppressive agents, e.g. cyclophosphamide (CYC) and imatinib (PDGFR inhibitor), might be useful for treating SSc-related ILD. Our objective was to evaluate the safety and efficacy of this combination therapy in scleroderma-related pulmonary disease. Methods. Five patients with advanced SSc-ILD underwent comprehensive cardiopulmonary evaluation, followed by administration of oral imatinib (200 mg/day) and intravenous CYC (500 mg every 3 weeks). Safety was assessed by close monitoring of complete blood count, liver and cardiac functions. Efficacy was evaluated by measuring pulmonary functions at 6 and 12 months. Results. Of the five patients in the study, four had severe and one had mild restrictive lung disease. All patients tolerated the combination treatment without myelosuppression, deterioration of liver functions or cardiac status. Only one patient had mild fluid overload requiring diuretics. Two patients completed 1 yr of treatment. Only the patient with mild restrictive lung disease showed improvement in pulmonary function. Conclusion. The combination of intravenous CYC and oral imatinib was well-tolerated without major side effects. Clinical improvement was seen in only the patient with mild restrictive disease. To our knowledge, this is the first study examining the safety, tolerability and efficacy of imatinib in combination with CYC in scleroderma-related pulmonary disease. Large prospective trials are needed to further determine optimal timing, dose and duration of this regimen.

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