title: Predicting treatment outcomes and responder subsets in scleroderma-related interstitial lung disease.
abstract: OBJECTIVE
  To identify baseline characteristics of patients with scleroderma-related interstitial lung disease (SSc-ILD) that could serve as predictors of the most favorable response to 12-month treatment with oral cyclophosphamide (CYC).
  
  
  METHODS
  Regression analyses were retrospectively applied to the Scleroderma Lung Study data in order to identify baseline characteristics that correlated with the absolute change in forced vital capacity (FVC) (% predicted values) and the placebo-adjusted change in % predicted FVC over time (the CYC treatment effect).
  
  
  RESULTS
  Completion of the CYC arm of the Scleroderma Lung Study was associated with a placebo-adjusted improvement in the % predicted FVC of 2.11% at 12 months, which increased to 4.16% when patients were followed up for another 6 months (P=0.014). Multivariate regression analyses identified the maximal severity of reticular infiltrates (assessed as maximum fibrosis scores) on high-resolution computed tomography (HRCT) at baseline, the modified Rodnan skin thickness score (MRSS) at baseline, and the Mahler baseline dyspnea index as independent correlates of treatment response. When patients were stratified on the basis of whether 50% or more of any lung zone was involved by reticular infiltrates on HRCT and/or whether patients exhibited an MRSS of at least 23, a subgroup of patients emerged in whom there was an average CYC treatment effect of 9.81% at 18 months (P<0.001). Conversely, there was no treatment effect (a -0.58% difference) in patients with less severe HRCT findings and a lower MRSS at baseline.
  
  
  CONCLUSIONS
  A retrospective analysis of the Scleroderma Lung Study data identified the severity of reticular infiltrates on baseline HRCT and the baseline MRSS as patient features that might be predictive of responsiveness to CYC therapy.
authors.affiliation: Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1690, USA. mroth@mednet.ucla.edu
authors.forename: Michael D
authors.initials: MD
authors.lastname: Roth
authors.forename: Chi-Hong
authors.initials: CH
authors.lastname: Tseng
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
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: Goldin
authors.forename: Dinesh
authors.initials: D
authors.lastname: Khanna
authors.forename: Eric C
authors.initials: EC
authors.lastname: Kleerup
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: David
authors.initials: D
authors.lastname: Elashoff
authors.forename: Robert M
authors.initials: RM
authors.lastname: Elashoff
mesh_terms: D000328:Adult; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D017563:Lung Diseases, Interstitial / Q000150:complications / Q000188:drug therapy*; D008297:Male; D012129:Respiratory Function Tests; D012595:Scleroderma, Systemic / Q000150:complications / Q000188:drug therapy*; D016896:Treatment Outcome; D014797:Vital Capacity
chemical_list: D018501:Antirheumatic Agents; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide