Effect of nintedanib on circulating biomarkers in subjects with systemic sclerosis-associated interstitial lung disease (SSc-ILD)* 

Background In the SENSCIS trial in subjects with SSc-ILD, nintedanib reduced the rate of decline in forced vital capacity (FVC) over 52 weeks by 44% compared with placebo.

Objective To investigate the effects of nintedanib on circulating biomarkers of extracellular matrix (ECM) turnover, epithelial injury and inflammation in the SENSCIS trial.

Methods Subjects had SSc with first non-Raynaud symptom in the prior≤7 years, extent of fibrotic ILD on high-resolution computed tomography (HRCT)≥10% and FVC≥40% predicted. Patients were randomised to receive nintedanib or placebo stratified by anti-topoisomerase I antibody (ATA). Blood samples were taken at baseline and at weeks 4, 24 and 52. Fold changes in adjusted mean levels of circulating biomarkers were analyzed using a linear mixed model for repeated measures. Data were log₁₀ transformed before analysis and estimates of change from baseline were back-transformed ([Abb. 1]).

Results A total of 576 subjects received trial drug (288 nintedanib, 288 placebo). A transient increase in fold change from baseline in C-reactive protein (CRP) (a marker of inflammation) was observed in subjects who received nintedanib versus placebo at week 4. After an initial increase at week 4 in the fold change from baseline in CRP degraded by MMP-1/8 (CRPM) (a marker of ECM turnover), a trend to decreasing levels was observed in subjects who received nintedanib compared with placebo at week 52. Decreases in the fold change from baseline in collagen 3 degraded by MMP-9 (C3M) and N-terminal propeptide of type VI collagen (pro-C6) (markers of ECM turnover) were observed in subjects who received nintedanib compared with placebo from week 24 and week 4, respectively. A decrease in fold change from baseline in Krebs von den Lungen-6 (KL-6) (a marker of epithelial injury) was observed in subjects who received nintedanib versus placebo at week 52. A decrease in fold change from baseline in cancer antigen 125 (CA-125) (a marker of epithelial injury) was observed in subjects who received nintedanib versus placebo from week 4 ([Abb. 1]).

Conclusions Data from the SENSCIS trial suggest that nintedanib reduced circulating levels of markers of ECM turnover and epithelial injury in subjects with SSc-ILD.

Abb. 1 Fold changes from baseline in biomakers over 52 weeks

Publication History

Article published online:
09 March 2023