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Background  Blood derived biomarkers have been extensively described as potential prognostic markers in idiopathic pulmonary fibrosis (IPF), but studies have been limited by analyses using data-dependent thresholds, inconsistent adjustment for confounders and an array of endpoints, thus often yielding ungeneralisable results. Meta-analysis of individual participant data (IPD) is a powerful tool to overcome these limitations. Through systematic review of blood derived biomarkers, sufficient studies with measurements of Matrix Metalloproteinase-7 (MMP-7) were identified to facilitate standardised analyses of the prognostic potential of this biomarker in IPF.    Methods  Electronic databases were searched on 12th 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 according to standardised MMP-7 z-scores, with a secondary outcome of disease progression in 12 months, all adjusted for age, gender, smoking and baseline FVC.    Results  IPD was available for nine studies out of twelve identified, reporting outcomes from 1664 participants. Baseline MMP-7 levels were associated with increased mortality risk (adjusted HR1.23, 95%CI 1.03;1.48, I 2 =64.3%) and disease progression (adjusted OR1.27, 95%CI 1.11;1.46, I 2 =5.9%). In limited studies, three-month change in MMP-7 was not associated with outcomes.    Conclusion  IPD meta-analysis demonstrated greater baseline MMP-7 levels were independently associated with an increased risk of poor outcomes in patients with untreated IPF, whilst short term changes did not reflect disease progression.

A systematic review of blood biomarkers with individual participant data meta-analysis of matrix metalloproteinase-7 in idiopathic pulmonary fibrosis