Fibrosis

In 2012, Richards et al. published a study that analyzed 92 potential biomarkers in an initial cohort of 140 patients with IPF, followed by validation with an independent cohort of 101 additional patients with IPF. The authors then developed and tested an integrated risk prediction score using a combination of protein markers and patient characteristics. 

The authors found that high concentrations of MMP-7 predicted poor overall survival, poor transplant-free survival, and poor progression-free survival in the initial patient cohort. In the independent validation cohort, high concentrations of MMP-7 predicted poor transplant-free survival and poor overall survival.

In 2018, Neighbors et al. published a post-hoc analysis of the test and replication cohorts from the CAPACITY 004, CAPACITY 006, and ASCEND phase III clinical trials of pirfenidone. For this analysis, the authors were interested in the predictive and prognostic qualities of 12 biomarkers in IPF, one of which was POSTN. The authors chose POSTN because it is expressed at elevated concentrations in tissue and blood from IPF patients. POSTN is also associated with IPF disease progression. 

However, higher baseline POSTN concentrations were associated with larger forced vital capacity (FVC) decline.

TN-C, an extracellular matrix protein expressed during wound healing, has been identified at elevated levels in the lungs of patients with IPF. Van der Velden et al. published a paper in 2016 that tested an experimental JNK inhibitor known as CC-930. Their phase II cohort study of IPF patients measured CC-930’s effect on TN-C levels as an exploratory endpoint. 

The mean predicted forced vital capacity (FVC) declined after patients took CC-930 for 26–32 weeks. The authors found that changes in patients’ TN-C levels significantly correlated with changes in predicted FVC. The same was true of patients’ MMP-7 and SP-D levels.