Presentation (CTI)

OBJECTIVES: SSc-ILD is a leading cause of mortality in systemic sclerosis, but mortality is rarely used as a primary trial endpoint due to the long follow-up required. Consequently, forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO) are widely used as surrogate markers of disease progression. This systematic literature review (SLR) evaluates their association with mortality in patients with SSc-ILD.
METHODS: Embase and MEDLINE® were searched in May 2026, from database inception, to identify studies reporting data on association of FVC/DLCO with mortality.
RESULTS: A total of 44 studies were included in this SLR, assessing the association between FVC and/or DLCO and all-cause or SSc-ILD-related mortality. Of these, six were interventional studies (including randomized controlled trials and real-world studies), and 38 were observational. FVC was reported heterogeneously, including baseline thresholds of <70% predicted (n=5), <80% predicted (n=2), and as a continuous % predicted measure (n=16). Baseline % predicted FVC was significantly associated with mortality, with multivariable HRs of 0.95-0.99 per 1% increase across six studies. Additionally, 24 studies assessed FVC decline, most commonly using thresholds of >5%, >10%, and >15%, with 15 reporting a significant association between worsening FVC and increased mortality risk. Similarly, baseline DLCO % predicted was significantly associated with mortality, with multivariable HRs ranging from 0.95-0.98 per 1% increase in three studies. Among interventional trials, SLS-1 and SLS-2 showed that declines in FVC and DLCO over 2 years were better predictors of mortality than baseline values.
CONCLUSIONS: Baseline percent-predicted FVC and DLCO, and their changes over time, predict mortality in SSc-ILD. However, heterogeneity in thresholds, endpoint definitions, and follow-up durations limits comparability. Standardized thresholds and prospective surrogacy validation are needed to strengthen the evidence.