Assessment of a relationship between prognostic biomarkers and treatment response in ISABELA1 &2 IPF cohorts

Abstract

<b>Background:</b> Idiopathic pulmonary fibrosis (IPF) is characterized by fibrosis, progressive loss of pulmonary function and poor survival. Matrix metalloproteinase-7 (MMP-7), a basaloid cell and pro-fibrotic macrophage marker, is a prognostic blood marker of disease progression and mortality in IPF. Blood biomarkers have not yet been used to stratify IPF patients in randomized controlled trials. Thus, patient heterogeneity may complicate interpretation of IPF clinical trial outcomes. <b>Aim:</b> Assess biomarker levels with respect to patient heterogeneity at baseline and clinical endpoints in ISABELA1 &amp;2 studies. <b>Methods:</b> Plasma collected longitudinally from 1280 IPF patients enrolled in ISABELA1 &amp;2 (NCT03711162; NCT03733444) was analyzed for 17 circulating soluble disease-related biomarkers. Statistical learning algorithms were used to evaluate relationships between biomarker levels, disease progression (first occurrence ≥10% decline in forced vital capacity [FVC] or mortality to 1 year) and pharmacotherapy. <b>Results:</b> Baseline biomarker levels were comparable across studies. Patients with an annual decline in FVC ≥10% had higher baseline MMP-7 (p&lt;0.005), whereas other analytes were not significantly different. Also, patients with baseline MMP-7 &gt;5.18 μg/L (computed median) had greater probability for disease progression (p&lt;0.0001). Analyses of a relationship between biomarker levels and treatment are ongoing. <b>Conclusion:</b> We confirm in two independent IPF cohorts that MMP-7 is a prognostic biomarker of disease progression. Biomarker-based enrichment strategies focused on MMP-7 levels may support stratification of patients with similar progression and enhance drug development in IPF.