A BIOMARKER analysis from the SENSCIS trial has revealed that elevated levels of a specific blood protein can identify patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) at higher risk of rapid lung function decline.
Researchers analysed data from the SENSCIS trial, which included patients with systemic sclerosis and seven years or fewer since their first non-Raynaud symptom. Candidate biomarkers of inflammation, epithelial dysfunction, and extracellular matrix synthesis and turnover were measured in serum or plasma.
Associations were assessed between baseline biomarker levels and decline in forced vital capacity over 52 weeks and change in modified Rodnan Skin Score at week 52 in the placebo group, alongside biomarker changes between the nintedanib and placebo groups.
Baseline Krebs von den Lungen-6 and citrullinated vimentin degraded by MMP-2/8 levels were significantly associated with the rate of decline in forced vital capacity over 52 weeks in uncorrected analyses. A baseline Krebs von den Lungen-6 concentration above 1000 U/mL, compared with 1000 U/mL or below, was associated with a greater rate of decline in forced vital capacity (p=0.009).
Higher baseline levels of N-terminal propeptide of type III collagen, chemokine (C-C motif) ligand 2, and C-reactive protein were significantly associated with less improvement in skin score at week 52, after correction for multiple comparisons.
Decreases in cancer antigen 125 and N-terminal propeptide of type VI collagen over 52 weeks were observed in patients who received nintedanib compared with placebo. In mediation analysis, 48.0% of the effect of nintedanib on change in lung function at week 52 was attributed to the treatment-related decrease in cancer antigen 125 at week 24.
These findings have suggested that applying a dichotomised threshold for Krebs von den Lungen-6 could help identify patients with systemic sclerosis-associated interstitial lung disease more likely to experience short-term progression. Nintedanib reduced levels of the epithelial dysfunction marker cancer antigen 125 and the collagen synthesis marker pro-C6. The authors have suggested these biomarkers could inform more practical, short-term risk stratification.
Reference
Assassi S et al. SENSCIS trial investigators. Circulating biomarkers in patients with systemic sclerosis–associated interstitial lung disease in the SENSCIS trial. Annals of the Rheumatic Diseases. 2026;DOI:10.1016/j.ard.2026.07.005.
Featured image: Kateryna on Adobe Stock
Each article is made available under the terms of the Creative Commons Attribution-Non Commercial 4.0 License.
