Current concepts in disease-modifying therapy for systemic sclerosis-associated interstitial lung disease: lessons from clinical trials

Curr Rheumatol Rep. 2009 Apr;11(2):111-9. doi: 10.1007/s11926-009-0016-2.


Interstitial lung disease (ILD) is the leading cause of mortality in patients with systemic sclerosis (SSc), which is also known as scleroderma. Two randomized clinical trials in patients with SSc-related ILD have shown that oral or intravenous cyclophosphamide is associated with modest but significant or near-significant improvements in lung function, dyspnea, and physical function. In addition, the Scleroderma Lung Study and an observational study showed that baseline forced vital capacity less than 70% and moderate fibrosis on thoracic high-resolution CT are predictors of response to cyclophosphamide therapy and/or survival, whereas active alveolitis on bronchoalveolar lavage is not. Newer therapies for SSc patients with ILD include mycophenolate mofetil, tyrosine kinase inhibitors (imatinib, dasatinib), and anti-interleukin-13 monoclonal antibody. Several uncontrolled trials have reported favorable results of mycophenolate mofetil in SSc-related ILD. A randomized double-blind controlled trial by the Scleroderma Lung Study Research Group is currently comparing the efficacy and safety of mycophenolate mofetil versus oral cyclophosphamide.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Antibodies, Blocking / therapeutic use
  • Antibodies, Monoclonal / therapeutic use
  • Antirheumatic Agents / therapeutic use*
  • Benzamides
  • Cyclophosphamide / therapeutic use
  • Dasatinib
  • Humans
  • Imatinib Mesylate
  • Immunosuppressive Agents / therapeutic use*
  • Interleukin-13 / immunology
  • Lung Diseases, Interstitial / drug therapy*
  • Lung Diseases, Interstitial / etiology
  • Lung Diseases, Interstitial / physiopathology
  • Mycophenolic Acid / analogs & derivatives
  • Mycophenolic Acid / therapeutic use
  • Piperazines / therapeutic use
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrimidines / therapeutic use
  • Randomized Controlled Trials as Topic
  • Respiratory Function Tests
  • Scleroderma, Systemic / complications
  • Scleroderma, Systemic / drug therapy*
  • Scleroderma, Systemic / physiopathology
  • Thiazoles / therapeutic use
  • Treatment Outcome


  • Antibodies, Blocking
  • Antibodies, Monoclonal
  • Antirheumatic Agents
  • Benzamides
  • Immunosuppressive Agents
  • Interleukin-13
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Thiazoles
  • Imatinib Mesylate
  • Cyclophosphamide
  • Mycophenolic Acid
  • Dasatinib