Objective. To identify specific clinical and serum protein biomarkers that are associated with longitudinal outcome of RA-associated interstitial lung disease（RA-ILD).Methods. 60 RA patients with clinical and serological profiles were assessed by HRCT and pulmonary function tests (PFTs) at baseline (Year 0) and 5 years post enrollment (Year 5). Progression versus non-progression was defined based on the changes in Quantitative Modified HRCT scores and PFTs over time. Specific serum protein biomarkers were assessed in serum samples at baseline and Year 5 by Multiplex enzyme-linked immunosorbent assays (ELISAs).Results. Based on changes of Quantitative Modified HRCT scores, 32% of patients demonstrated progressive RA-ILD, 35% were stable, and 33% improved. Baseline age and rheumatoid factor (RF) were significantly different between RA-ILD outcomes of progression versus no-progression (p=0.002 and 0.027, respectively). In multivariate analyses, changes in the serum levels of CXCL11/I-TAC and MMP13 from Year 0 to Year 5 (log Year 5-log Year 0) also distinguished RA-ILD outcomes (p< 0.05). A final binary logistic regression model revealed that baseline age and changes of MMP13 were associated with RA-ILD progression (Yes vs. No) at Year 5 (p< 0.05). Receiver Operating Characteristics analysis indicated that these variables predicted progression with an AUC of 0.7569.Conclusion. While baseline age and RF predicted RA-ILD outcomes of progression versus no-progression, changed levels of CXCL11/I-TAC and MMP-13 over 5 years were also correlated with long-term prognosis of RA-ILD. In multivariate analyses, baseline age and changed levels of MMP-13 were associated with the risk of progression of RA-ILD.Trial registrationNo