Early Radiographic Progression of Scleroderma: Lung Disease Predicts Long-term Mortality

Elizabeth R Volkmann; Donald P Tashkin; Michael D Roth; Jonathan Goldin; Grace H J Kim

doi:10.1016/j.chest.2021.11.033

Early Radiographic Progression of Scleroderma: Lung Disease Predicts Long-term Mortality

Chest. 2022 May;161(5):1310-1319. doi: 10.1016/j.chest.2021.11.033. Epub 2021 Dec 8.

Authors

Elizabeth R Volkmann¹, Donald P Tashkin², Michael D Roth², Jonathan Goldin³, Grace H J Kim³

Affiliations

¹ Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA. Electronic address: evolkmann@mednet.ucla.edu.
² Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA.
³ Department of Radiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA.

Abstract

Background: Radiographic end points commonly are included in therapeutic trials for systemic sclerosis (SSc)-interstitial lung disease (ILD); however, the relationship between these outcomes and long-term mortality is unclear.

Research question: Do short-term changes in radiographic measures of ILD predict long-term survival in patients with SSc?

Study design and methods: The Scleroderma Lung Study (SLS) I and II evaluated the safety and efficacy of cyclophosphamide (in SLS I and II) and mycophenolate mofetil (in SLS II) for the treatment of SSc-ILD. Changes in the extent of ILD over time were assessed on high-resolution CT scans of the chest by quantitative image analysis, an approach that applies a computer-based algorithm to assess changes in the radiographic extent of ILD objectively. Participants subsequently were followed for up to 12 years (SLS I) and 8 years (SLS II). Cox proportional hazards models determined whether the change in the quantitative radiographic extent of ILD predicted survival, adjusting for other known predictors of survival.

Results: Among SLS I and II participants, 82 and 90 had follow-up imaging scans, respectively, and were included in the analysis. Participants in both trials who showed an increase in the total quantitative radiographic extent of ILD scores of ≥ 2% at 12 months (SLS I) or 24 months (SLS II) experienced significantly worse long-term survival than those with change scores of < 2% (P ≤ .01, log-rank test). In the multivariate Cox models, radiographic progression remained associated with worse long-term survival in SLS I (P = .089) and SLS II (P = .014).

Interpretation: Data from two independent clinical trial cohorts with extensive long-term follow-up demonstrated that radiographic progression of ILD over 12 to 24 months, in both treatment and placebo arms, can predict increased risk for long-term mortality in patients with SSc. These findings suggest that radiographic end points may serve as surrogates for mortality in SSc-ILD.

Keywords: biomarkers; interstitial lung disease; mortality; systemic sclerosis.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Disease Progression
Humans
Immunosuppressive Agents / therapeutic use
Lung
Lung Diseases, Interstitial* / complications
Lung Diseases, Interstitial* / etiology
Mycophenolic Acid / therapeutic use
Scleroderma, Systemic* / complications
Scleroderma, Systemic* / diagnostic imaging
Scleroderma, Systemic* / drug therapy
Vital Capacity

Substances

Immunosuppressive Agents
Mycophenolic Acid

Abstract

Publication types

MeSH terms

Substances

Grants and funding