# Circulating biomarkers in subjects with progressive pulmonary fibrosis: data from the INBUILD trial

## TL;DR

The study found that the drug nintedanib lowers specific blood markers linked to lung damage in patients with progressive pulmonary fibrosis.

## Contribution

The study shows that nintedanib reduces circulating levels of epithelial dysfunction markers like CA-125 in progressive pulmonary fibrosis patients.

## Key findings

- Baseline s-ICAM levels were significantly associated with faster FVC decline and ILD progression or death.
- Nintedanib significantly reduced levels of KL-6, SP-D, CA-125, and CA19-9 compared to placebo.
- 16.4% of nintedanib's effect on FVC improvement was mediated by reduced CA-125 levels.

## Abstract

We investigated the prognostic potential of circulating biomarkers at baseline and the effects of nintedanib on changes in these biomarkers in subjects with progressive pulmonary fibrosis (PPF).

In the INBUILD trial, subjects with PPF received nintedanib (n=332) or placebo (n=331). Associations between biomarker levels at baseline and the rate of forced vital capacity (FVC) decline (mL·year−1) over 52 weeks, time to interstitial lung disease (ILD) progression (absolute decline in FVC % predicted ≥10%) or death over 52 weeks, time to first acute exacerbation or death over the whole trial, and time to death over the whole trial were assessed in the placebo group. Changes in adjusted mean levels of biomarkers in the nintedanib and placebo groups were assessed using linear mixed models for repeated measures. Biomarker data were log2 transformed prior to analysis. Analyses were corrected for multiplicity.

Baseline level of s-ICAM was significantly associated with rate of FVC decline and time to ILD progression or death over 52 weeks in the placebo group. No biomarker was significantly associated with time to first acute exacerbation or death or time to death. Decreases in Krebs von den Lungen-6 (KL-6), surfactant protein D (SP-D), CA-125 and CA19-9 were observed in subjects who received nintedanib versus placebo over 52 weeks. The largest decrease was in CA-125. In a mediation analysis, 16.4% of the effect of nintedanib on change in FVC at week 52 was attributed to the treatment-related decrease in CA-125 at week 12.

In subjects with PPF, nintedanib reduced circulating CA-125 and, to a lesser extent, other markers of epithelial dysfunction.

In a randomised controlled trial in subjects with progressive pulmonary fibrosis, nintedanib reduced circulating levels of markers of epithelial dysfunction, particularly CA-125, versus placebo
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