Performance of an Idiopathic Pulmonary Fibrosis Derived Multibiomarker Panel for Rheumatoid Arthritis-Associated Interstitial Lung Disease.

Abstract

OBJECTIVE To assess whether a panel of peripheral blood biomarkers associated with idiopathic pulmonary fibrosis (IPF) is also associated with interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) utilizing three independent cohorts. METHODS We first assessed the association of a panel of IPF-associated biomarkers with prevalent ILD among two separate RA cohorts (n=93 and n=71). Concentrations of eight IPF-related biomarkers (eotaxin, Flt-3L, IL-8, MDC, MCP-1, and MMP-2/7/9) were measured, standardized, and summed to generate a multibiomarker score. We subsequently validated the association of this score (minus MMP-2) with prevalent and incident ILD in an independent multicenter, prospective cohort of US Veterans with RA (n=2,507). Multivariable regression models were adjusted for relevant covariates in the validation cohort. RESULTS In both development cohorts, participants with RA-ILD had significantly higher IPF multibiomarker scores than those with RA alone. In the independent validation cohort, participants with the highest quartile multibiomarker scores had a significantly higher likelihood of prevalent ILD (adjusted odds ratio 2.14 [95% CI 1.18-3.87]) and incident ILD (adjusted hazard ratio 2.45 [95% CI 1.55-3.88]) than those in the lowest quartile. The cumulative hazard of incident ILD approached 20% by 15 years for those in the highest quartile compared to <10% for all other quartiles. CONCLUSION A multibiomarker panel derived from IPF-associated biomarkers was associated with RA-ILD in separate development and validation cohorts. This overlap supports the concept of shared etiopathogenesis of IPF and RA-ILD and illustrates the potential for peripheral blood biomarker panels to stratify ILD risk among RA patients.