ANTI-FIBROTIC THERAPY MODULATES MORTALITY RISK ASSOCIATED WITH CIRCULATING PLASMA BIOMARKERS IN PATIENTS WITH IDIOPATHIC PULMONARY FIBROSIS

Abstract

SESSION TITLE: IPF: From Diagnosis to Treatment SESSION TYPE: Original Investigations PRESENTED ON: 10/21/2019 1:30 PM - 2:30 PM PURPOSE: A number of circulating plasma biomarkers have been associated with differential mortality risk in patients with idiopathic pulmonary fibrosis (IPF). The studies performed identifying these biomarkers were largely performed prior to the approval of anti-fibrotic therapies. The purpose of this investigation was to determine whether anti-fibrotic medications modulated the survival association of these known biomarkers. METHODS: Patients followed at UC-Davis and the University of Chicago who met international consensus criteria for IPF and provided a blood sample were included in the analysis. Circulating levels of CA-125, CXCl-13, MMP-7, SPD, YKL-40, MMP-1 and VCAM-1 were determined using a Luminex multiplex assay. Using 24-month transplant-free survival as the endpoint, exploratory analysis was conducted to identify stratification values for each biomarker. Cox regression was then performed to determine mortality risk associated with each biomarker in anti-fibrotic exposed and unexposed patients. RESULTS: Two hundred ninety-three patients with IPF were included in the analysis, including 70 exposed to anti-fibrotic therapy. Median follow-up time was 12 months and 92 (30%) patients died during the follow-up period. Increased levels of CXCl-13, MMP-7, SPD, YKL-40, MMP-1 and VCAM-1 were associated with increased mortality risk in untreated patients, but not in those receiving anti-fibrotic therapy. The biomarker with the strongest differential mortality association was MMP-7. Those with high MMP-7 levels not exposed to anti-fibrotic therapy had increased mortality risk (HR 2.48, 95% CI 1.50-4.09; p<0.001), while anti-fibrotic exposed patients had a trend towards decreased mortality risk (HR 0.47, 95% CI 0.18-1.19; p=0.1). CONCLUSIONS: Previously identified plasma biomarkers predictive of mortality in patients with IPF do not predict mortality in those treated with anti-fibrotic therapy. Some biomarkers, such as MMP-7 displayed a trend towards decreased mortality risk in anti-fibrotic exposed patients. CLINICAL IMPLICATIONS: Exposure to anti-fibrotic therapy appears to modulate the mortality risk associated with known biomarkers of IPF outcomes. These data raise the question of whether such biomarkers are of value in the era of anti-fibrotic therapy. DISCLOSURES: Speaker/Speaker's Bureau relationship with Boehringer Ingelheim Please note: $5001 - $20000 Added 03/16/2019 by Ayodeji Adegunsoye, source=Web Response, value=Honoraria Grant funding relationship with Boehringer Ingelheim Please note: $20001 - $100000 Added 03/16/2019 by Ayodeji Adegunsoye, source=Web Response, value=Grant/Research no disclosure on file for Shehabaldin Alqalyoobi; No relevant relationships by Noelle Boctor, source=Web Response no disclosure on file for Cara Hrusch; No relevant relationships by Angela Linderholm, source=Web Response no disclosure on file for Imre Noth; Advisory Committee Member relationship with Genentech Please note: $1001 - $5000 Added 03/15/2019 by Justin Oldham, source=Web Response, value=Consulting fee Speaker/Speaker's Bureau relationship with Genentech Please note: $5001 - $20000 Added 03/15/2019 by Justin Oldham, source=Web Response, value=Honoraria Advisory Committee Member relationship with Boehringer Ingelheim Please note: $5001 - $20000 Added 03/15/2019 by Justin Oldham, source=Web Response, value=Consulting fee Speaker/Speaker's Bureau relationship with Boehringer Ingelheim Please note: $5001 - $20000 Added 03/15/2019 by Justin Oldham, source=Web Response, value=Honoraria No relevant relationships by Janelle Pugashetti, source=Web Response No relevant relationships by Anne Sperling, source=Web Response Advisory Committee Member relationship with Boehringer Ingelheim Please note: $1001 - $5000 Added 11/30/2018 by Mary Strek, source=Web Response, value=Consulting fee Consultant relationship with Boehringer Ingelheim Please note: $5001 - $20000 Added 11/30/2018 by Mary Strek, source=Web Response, value=Consulting fee Speaker/Speaker's Bureau relationship with Boehringer Ingelheim Please note: $5001 - $20000 Added 11/30/2018 by Mary Strek, source=Web Response, value=Honoraria PI relationship with Boehringer Ingelheim Please note: >$100000 Added 11/30/2018 by Mary Strek, source=Web Response, value=Grant/Research PI relationship with Novartis Please note: $5001 - $20000 Added 11/30/2018 by Mary Strek, source=Web Response, value=Grant/Research Support