Short-term progression of interstitial lung disease in systemic sclerosis predicts long-term survival in two independent clinical trial cohorts

Ann Rheum Dis. 2019 Jan;78(1):122-130. doi: 10.1136/annrheumdis-2018-213708. Epub 2018 Nov 8.


Objective: To assess survival and identify predictors of survival in patients with systemic sclerosis-interstitial lung disease (SSc-ILD) who participated in the Scleroderma Lung Studies (SLS) I and II.

Methods: SLS I randomised 158 patients with SSc-ILD to 1 year of oral cyclophosphamide (CYC) vs placebo. SLS II randomised 142 patients to 1 year of oral CYC followed by 1 year of placebo vs 2 years of mycophenolate mofetil. Counting process Cox proportional hazard modelling identified variables associated with long-term mortality in SLS I and II. Internal validation was performed using joint modelling.

Results: After a median follow-up of 8 years, 42% of SLS I patients died, and when known the cause of death was most often attributable to SSc. There was no significant difference in the time to death between treatment arms in SLS I or II. Higher baseline skin score, older age, and a decline in the forced vital capacity (FVC) and the diffusing capacity for carbon monoxide (DLCO) over 2 years were independently associated with an increased risk of mortality in SLS I. The Cox model identified the same mortality predictor variables using the SLS II data.

Conclusion: In addition to identifying traditional mortality risk factors in SSc (skin score, age), this study demonstrated that a decline in FVC and DLCO over 2 years was a better predictor of mortality than baseline FVC and DLCO. These findings suggest that short-term changes in surrogate measures of SSc-ILD progression may have important effects on long-term outcomes.

Keywords: interstitial lung disease; survival; systemic sclerosis; treatment.

Publication types

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

MeSH terms

  • Adult
  • Carbon Monoxide / analysis
  • Cyclophosphamide / administration & dosage*
  • Disease Progression
  • Drug Administration Schedule
  • Female
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Lung Diseases, Interstitial / drug therapy
  • Lung Diseases, Interstitial / etiology
  • Lung Diseases, Interstitial / mortality*
  • Male
  • Middle Aged
  • Mycophenolic Acid / administration & dosage*
  • Proportional Hazards Models
  • Pulmonary Diffusing Capacity
  • Risk Factors
  • Scleroderma, Systemic / complications
  • Scleroderma, Systemic / drug therapy
  • Scleroderma, Systemic / mortality*
  • Skin / pathology
  • Time Factors
  • Treatment Outcome
  • Vital Capacity


  • Immunosuppressive Agents
  • Carbon Monoxide
  • Cyclophosphamide
  • Mycophenolic Acid