Current concepts in disease-modifying therapy for systemic sclerosis-associated interstitial lung disease: lessons from clinical trials.
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.
Au
Karen
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Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA.
Khanna
Dinesh
D
Clements
Philip J
PJ
Furst
Daniel E
DE
Tashkin
Donald P
DP
D019138:Antibodies, Blocking / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001549:Benzamides; D003520:Cyclophosphamide / Q000627:therapeutic use; D000069439:Dasatinib; D006801:Humans; D000068877:Imatinib Mesylate; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D018793:Interleukin-13 / Q000276:immunology; D017563:Lung Diseases, Interstitial / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D010879:Piperazines / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012129:Respiratory Function Tests; D012595:Scleroderma, Systemic / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D013844:Thiazoles / Q000627:therapeutic use; D016896:Treatment Outcome
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D001549:Benzamides; D007166:Immunosuppressive Agents; D018793:Interleukin-13; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D003520:Cyclophosphamide; D009173:Mycophenolic Acid; D000069439:Dasatinib