| Summary: | We aimed to validate quantitative high-resolution computed tomography (HRCT) imaging analyses of interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients, and to delineate a broad spectrum of annual longitudinal changes of ILD severity in the RA-ILD cohorts. Retrospective cohort 1 (<i>n</i> = 26) had matched PFT results and prospective cohort 2 (<i>n</i> = 34) were followed for over two years with baseline serum specimen. Automated quantitative analysis of HRCT was expressed as the extent of ground-glass opacity, lung fibrosis, honeycombing, and their summation—the total extent of quantitative ILD (QILD). Higher QILD score was associated with lower pulmonary function especially for DLCO% (ρ = −0.433, <i>p</i> = 0.027). Higher serum level of Krebs von den Lungen 6 were significantly associated with high QILD scores (ρ = 0.400, <i>p</i> = 0.026). Regarding QILD score changes in whole lung, even a single point increase was significantly associated with interval progression detected by the radiologist. Four distinct patterns (improvement, worsening, convex-like, and concave-like) during the 24 months were described by QILD scores. Prolonged disease duration of ILD at baseline was significantly associated with worsening of QILD scores. QILD has the potential to reliably evaluate the dynamic severity changes in patients with RA-ILD.
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