title: Current concepts in disease-modifying therapy for systemic sclerosis-associated interstitial lung disease: lessons from clinical trials.
abstract: 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.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Au
authors.forename: Dinesh
authors.initials: D
authors.lastname: Khanna
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Clements
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Furst
authors.forename: Donald P
authors.initials: DP
authors.lastname: Tashkin
mesh_terms: 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
chemical_list: 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