Predicting treatment outcomes and responder subsets in scleroderma-related interstitial lung disease

Arthritis Rheum. 2011 Sep;63(9):2797-808. doi: 10.1002/art.30438.

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.

Conclusion: 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.

Trial registration: ClinicalTrials.gov NCT00004563.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Antirheumatic Agents / therapeutic use*
  • Cyclophosphamide / therapeutic use*
  • Double-Blind Method
  • Female
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Lung Diseases, Interstitial / complications
  • Lung Diseases, Interstitial / drug therapy*
  • Male
  • Respiratory Function Tests
  • Scleroderma, Systemic / complications
  • Scleroderma, Systemic / drug therapy*
  • Treatment Outcome
  • Vital Capacity

Substances

  • Antirheumatic Agents
  • Immunosuppressive Agents
  • Cyclophosphamide

Associated data

  • ClinicalTrials.gov/NCT00004563