B77-16 Antifibrotic Drug Use Influences the Association Between Pro-C3 and Risk of Mortality or Disease Progression in Patients With Idiopathic Pulmonary Fibrosis

Rationale Idiopathic pulmonary fibrosis (IPF) is characterized by accumulation of collagen-rich extracellular matrix (ECM) in the lung parenchyma. Pro-C3 is a neoepitope that reflects synthesis of type III collagen and has been investigated as a prognostic biomarker in IPF. In studies performed primarily in antifibrotic drug-naïve cohorts, higher Pro-C3 has been associated with an increased risk of mortality and disease progression in patients with IPF. We examined the relationship between Pro-C3 and mortality or disease progression in the IPF-PRO Registry. Methods The cohort (n = 914) came from the IPF-PRO Registry, which enrolled participants with IPF that was diagnosed or confirmed at the enrolling center in the prior 6 months. Pro-C3 was measured in enrollment serum using the Roche Diagnostics Elecsys® PRO-C3 assay. Cox models were used to test the association of Pro-C3 with a) time to death or lung transplant and b) time to disease progression (≥10% decline in FVC % predicted, death, or lung transplant). Models were adjusted for age, sex, FVC % predicted, DLCO % predicted, and antifibrotic drug use (nintedanib, pirfenidone, none) at enrollment. Interaction terms were included to determine if the relationship between Pro-C3 and outcomes differed by strata of antifibrotic drug use at enrollment. Results The cohort was 74.6% male with a mean (SD) age of 69.7 (7.8) years. At enrollment, mean FVC % predicted and DLCO % predicted were 72.7 (17.8) and 42.6 (14.6), respectively. About half of the cohort used antifibrotic therapy at enrollment (26.3% [n = 240] pirfenidone and 21.8% [n = 199] nintedanib). Over a median follow-up of 3.1 years, 514 patients experienced death or transplant and 643 patients experienced disease progression. In adjusted analyses, Pro-C3 was not associated with mortality or progression in the overall cohort, but treatment status was a significant effect modifier (Figure). Among patients taking antifibrotic therapy at enrollment, higher Pro-C3 was associated with a numerically lower risk of both outcomes, but there was no relationship between Pro-C3 and outcomes in patients not taking antifibrotic therapy at enrollment (Figure). Conclusions In a contemporary cohort of patients with IPF, the relationship between Pro-C3 levels and outcome varied dependent on treatment with antifibrotic agents. These findings highlight the importance of considering antifibrotic drug use when interpreting biomarker data. This abstract is funded by: The IPF-PRO/ILD-PRO Registry is supported by Boehringer Ingelheim Pharmaceuticals, Inc and run in collaboration with the Duke Clinical Research Institute and enrolling centers.