• Elizabeth R Volkmann, Donald P Tashkin, Michael D Roth, Jonathan Goldin, and Grace H J Kim.
• Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA. Electronic address: evolkmann@mednet.ucla.edu.
• Chest. 2022 May 1; 161 (5): 131013191310-1319.

BackgroundRadiographic 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 QuestionDo short-term changes in radiographic measures of ILD predict long-term survival in patients with SSc?Study Design And MethodsThe 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.ResultsAmong 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).InterpretationData 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.Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

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