Gastroesophageal reflux disease is associated with a more severe interstitial lung disease in systemic sclerosis in the EUSTAR cohort

Rheumatology (Oxford). 2025 Jan 8:keaf016. doi: 10.1093/rheumatology/keaf016. Online ahead of print.

Abstract

Objectives: Gastroesophageal reflux disease (GERD) is frequent in systemic sclerosis (SSc) and could predict progression of interstitial lung disease (ILD). We aimed to analyse (1) the prevalence of GERD among SSc-ILD patients, (2) its association with disease characteristics and (3) predictive factors for ILD progression in SSc-ILD patients with GERD.

Methods: SSc patients from the EUSTAR database with ILD were included. GERD was labeled as present if reflux/dysphagia was reported at the baseline visit or before. Disease characteristics of patients with and without GERD were compared at baseline. ILD progression was defined as relative FVC decline ≥10% or relative FVC decline between 5-9% in association with relative DLCO decline of ≥ 15% over 12±3 months of follow-up. Prognostic factors for ILD progression, overall survival and progression-free survival in SSc-ILD patients with GERD were tested by multivariable Cox regression.

Results: 5462 SSc-ILD patients were included, 4400 (80.6%) had GERD. Patients with GERD presented more frequently with diffuse cutaneous SSc (OR: 1.44 [1.22-1.69], p < 0.001) and more severe lung involvement with lower FVC (85.8±22.1 vs 90.2±20.1, p < 0.001), lower DLCO (60.8±19.7 vs 65.3±20.6, p < 0.001) and worse performance at the 6-minute walking test. Female sex (HR: 1.39 [1.07-1.80], p = 0.012) and older age (HR: 1.02 [1.01-1.03], p < 0.001) independently predicted ILD progression in SSc-ILD patients with GERD.

Conclusion: SSc-ILD patients with GERD appear to suffer from a more severe SSc disease. In this population, female sex may be considered as risk factor for ILD progression.

Keywords: gastroesophageal reflux disease; interstitial lung disease; progression; systemic sclerosis.