Short-Term Progression of Interstitial Lung Disease in Systemic Sclerosis Predictive of Long-Term Survival

Illustration of the lungs
Illustration of the lungs
A decline in FVC and DLCO over 2 years was a better predictor of mortality than baseline FVC and DLCO.

According to study data published in Annals of the Rheumatic Diseases, a decline in forced vital capacity (FVC) and the diffusing capacity for carbon monoxide (DLCO) over 2 years was predictive of mortality among patients with systemic sclerosis-interstitial lung disease (SSc-ILD).

Participants enrolled in the Scleroderma Lung Study I (SLS I) and the Scleroderma Lung Study II (SLS II) were eligible to participate in the present long-term follow-up study. The SLS I and SLS II cohorts comprised adult patients with SSc and evidence of ILD according to high-resolution computed tomography of the lungs. Participants had a disease duration ≤7 years from first non-Raynaud SSc symptom onset. In SLS I, 158 participants were randomly assigned to 1 year of oral cyclophosphamide vs 1 year of placebo. In SLS II, 142 patients were randomly assigned to 1 year of placebo vs 2 years of mycophenolate mofetil. According to the SLS I and SLS II protocol, patients were assessed for FVS and DLCO every 3 months for the 24-month study periods. Quantitative imaging analysis was also performed to quantify the extent of ILD in participants. For the present study, investigators collected long-term follow-up data on SLS I and II participants through their associated clinical centers. A mortality and morbidity committee was created to identify causes of death observed in deceased patients.

After a median follow-up of 8 years, 42% of those who participated in SLS I had died, with cause of death most often attributable to SSc. Additionally, 8 years after the first patient was randomly assigned in SLS II, 21% of participants had died, and 58% of deaths with known cause were attributable to SSc. According to Cox proportional hazards models, higher baseline skin score, older age, and decline in FVC and the DLCO over 2 years were independently associated with an increased risk for mortality in SLS I. In the SLS II study, increased age and increased baseline extent of cutaneous sclerosis (modified Rodnan skin score) were each independently associated with mortality. In addition, the change in FVC from baseline to 12 months predicted long-term survival (P <.05) but change in DLCO from baseline to 12 months did not. In an adjusted model accounting for the covariates of modified Rodnan skin score and age, an FVC decline ≥10% at 12 months and FVC decline ≥15% at 12 months were each associated with long-term survival in SLS II. Overall, similar risk factors for mortality were identified by Cox proportional hazards models in both study cohorts.

Related Articles

In additional to identifying traditional mortality risk factors in SSc, these data indicate that a decline in FVC and DLCO over 2 years is a strong predictor of mortality, more so than FVC and DLCO at baseline. These findings suggest that short-term changes in these surrogate measures of SSC-ILD progression may be important indicators of long-term outcomes. SSc providers should monitor patients with ILD closely to capture any early decline in lung function and administer the appropriate intervention.

follow @RheumAdvisor


Volkmann ER, Tashkin DP, Sim M, et al. Short-term progression of interstitial lung disease in systemic sclerosis predicts long-term survival in two independent clinical trial cohorts [published online November 8, 2018]. Ann Rheum Dis. doi:10.1136/annrheumdis-2018-213708