MMP7 predicts progression, death in antifibrotic-treated IPF patients

Higher levels of matrix metalloprotease 7 (MMP7) pretreatment are predictive of 12-month progression and mortality among patients with idiopathic pulmonary fibrosis (IPF) who have been treated with antifibrotics, reveals a recent study.

Both progressive and stable patients show increased MMP7 levels at 12 months, but the former consistently has higher MMP7 levels than the latter at all timepoints.

“Additionally, we demonstrate that categorical levels of MMP7 are associated with progression and mortality, thus bringing this biomarker closer to clinical use,” the researchers said.

Ninety-eight patients from the Australian Idiopathic Pulmonary Fibrosis Registry were included in this study. Serum was collected from participants at four timepoints over 1 year following antifibrotic treatment and analysed as two separate cohorts. Ten molecules of interest were assessed using enzyme linked immunosorbent assay or ELISA.

The research team stratified patients as either stable or progressive if they experienced ≥10-percent decline in forced vital capacity (FVC) or ≥15-percent decline in diffusing capacity for carbon monoxide (DLCO) or were deceased within 1 year of treatment initiation.

Predictor

At baseline, MMP7 levels were higher in progressive than stable patients in both groups (cohort 1: p=0.02; cohort 2: p=0.0002). Likewise, baseline MMP7 levels best differentiated progressive patients from those who were stable (cohort 1: area under curve [AUC], 0.74; p=0.02; cohort 2: AUC, 0.81; p=0.0003). [Respirology 2025;30:504-514]

In regression analysis of the combined cohort, increased levels of MMP7 significantly correlated with 12-month progression (odds ratio, 1.530; p=0.010) and a higher risk of overall mortality (hazard ratio, 1.268; p=0.002).

In addition, LASSO regression identified a multi-biomarker panel (MMP7, intercellular adhesion molecule 1 [ICAM-1], chitinase-3-like protein 1 [CHI3L1], and mucin 16 [CA125]) that more accurately differentiated progression compared with MMP7 alone.

Moreover, combining gender, age, physiology (GAP) with MMP7, ICAM-1, C-C chemokine motif ligand 18 (CCL18), and surfactant protein D (SP-D) showed better capacity in predicting 3-year mortality when compared with GAP alone.

“MMP7 along with a multi-biomarker and GAP panel can predict IPF progression and mortality, with the potential for optimizing management,” the researchers said.

Literature

These findings support those of previous studies that found an inverse longitudinal association between MMP7 and FVC. This relationship shows the potential of MMP7 as a predictor of decline in IPF. [ERJ Open Research 2017;3:00074-2016; Respirology 2017;22:486-493]

However, these studies were conducted in treatment-naïve patients and lacked longitudinal data, according to the researchers. One earlier study that included antifibrotic-treated IPF patients also found that higher MMP7 levels predicted worse survival. [Chest 202;158:1526-1534]

Other studies of biomarkers to guide therapy have failed to show utility. Further research is warranted to determine the clinical application of MMP7, according to the researchers. [Lancet Respiratory Medicine 2019;7:771-779]

“Our study supports the use of baseline and serial serum MMP7 levels as a predictive marker of IPF progression in antifibrotic-treated patients and identifies CA125 as a potential marker of stability,” the researchers said.

“Larger studies are required to determine how MMP7 and CA125 can be used to assist with clinical decision making,” they added.