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.