An individual participant data meta-analysis of prognostic blood biomarkers in IPF

ABSTRACT Background Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with variable disease trajectory. Blood biomarkers reflecting disease severity that can accurately predict outcomes are urgently needed. Through systematic review and meta-analysis, we evaluate the prognostic potential of matrix-metalloproteinase-7 (MMP-7) and other frequently studied blood biomarkers in patients with IPF. Methods Electronic databases were searched on 12 th November 2020 to identify prospective studies reporting outcomes in patients with untreated IPF, stratified according to at least one pre-specified biomarker, measured at either baseline or change over three months. Individual participant data (IPD) was sought for studies investigating MMP-7 as a prognostic factor. The primary outcome was overall mortality, with secondary outcomes including disease progression, defined as >10% relative FVC decline or death. Results 29 studies reporting outcomes from 3950 IPF participants were included, investigating a total of 16 biomarkers. IPD from MMP-7 studies was available for eleven cohorts. Baseline MMP-7 levels were associated with increased mortality (adjusted HR1.23 per SD increase, 95%CI 1.03;1.48, I 2 =64.3%) and disease progression (adjusted OR1.27 per SD increase, 95%CI 1.11;1.46, I 2 =5.9%), but change in MMP-7 over three-months was not associated with any of the measured outcomes. There was insufficient data for quantitative analysis in non-MMP7 studies, and whilst many biomarkers showed an association with clinical outcomes, replication of effects across studies was weak. Conclusion Baseline MMP-7 levels were associated with an increased risk of overall mortality and disease progression in patients with untreated IPF. The evidence for other biomarkers is currently insufficient with further studies needed.