Lung function and skin fibrosis changes as predictors of survival in SSc-associated interstitial lung disease: a EUSTAR study

Objectives This study assessed how changes in lung function, skin fibrosis and digital ulceration (DU) burden predict mortality in patients with SSc-associated interstitial lung disease (SSc-ILD), the leading cause of death in SSc. Methods Adult SSc-ILD patients from the European Scleroderma Trials and Research (EUSTAR) database enrolled since January 2009 with a date of diagnosis, a follow-up visit for change evaluation within 12 months plus a further visit or mortality information were eligible. Twelve-month changes in lung function (per cent predicted forced vital capacity [FVC%pred] and diffusing capacity of the lungs for carbon monoxide [DLCO%pred]), modified Rodnan skin score (mRSS) and change in DU burden were assessed for associations with survival, using multivariable Cox regression analyses adjusted for age, sex, smoking status and immunosuppressive therapy. Results Of 893 SSc-ILD patients included, 94 (10.5%) died over a mean follow-up of 39.0 ± 23.9 months. Absolute deterioration in FVC >10%pred within 12 months (n = 78/638 evaluable) was predictive for decreased survival (hazard ratio [HR] 3.81; 95% CI 1.67-8.66), as were composite measures combining (i) >10% FVC decline or mRSS worsening (HR 2.82; 95% CI 1.43-5.56) and (ii) FVC decline ≥10% or 5-9% with DLCO decline ≥15% (HR 3.42; 95% CI 1.68-7.00), but not changes in DLCO, mRSS or DU burden alone. Conclusions Changes in lung function and skin fibrosis within 12 months should be considered when evaluating risk of mortality. The effect of pharmacological treatments aiming at stabilization of these variables should be evaluated prospectively in clinical trials.