The Value of Biomarkers as Predictors of Outcome in Patients with Rheumatoid Arthritis-Associated Usual Interstitial Pneumonia

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Young Seok Lee
Ho Cheol Kim
Bo Young Lee
Chang Keun Lee
Mi-Young Kim
Se Jin Jang
Hye Sun Lee
Jieun Moon
Thomas V. Colby
Dong Soon Kim


Biomarkers, Rheumatoid arthritis, Interstitial lung disease, Prognosis, KL-6, IL-6


Background: Because of the highly variable clinical course of rheumatoid arthritis-associated usual interstitial pneumonia (RA-UIP), the prediction of patient prognosis is important. Objective: The aim of this study was to investigate the role of blood biomarkers as prognostic predictors in the patients with RA-UIP. Methods: The blood levels of biomarkers (Krebs von den Lungen-6 [KL-6], surfactant protein-A [SP-A], matrix metalloproteinase-7 [MMP-7], interleukin-6 [IL-6], and interleukin-32 [IL-32]) were retrospectively compared with the clinical courses of 62 patients with RA-UIP. Results: The median follow-up period was 33.4 months. RA-UIP progressed in 15 patients (45.2%) during one year of follow-up. We found that KL-6 and IL-6 were significant predictors of short-term (1 year) prognosis. Multivariate logistic regression analysis showed that the odds ratio (OR) for KL-6 was 1.001 (95% confidence interval [CI]: 1.000–1.003, p = 0.077) and that the OR for IL-6 was 1.040 (95% CI: 1.002–1.080, p = 0.039) for short-term disease progression. The addition of KL-6 and IL-6 to the clinical parameters (concordance index [C-index]: 0.958, p = 0.053) predicted short-term disease progression better than the clinical parameter alone (C-index: 0.853). In addition, patients with high levels of KL-6 (≥933 U/mL) had shorter survival than those with low levels of KL-6 (<933 U/mL) (median survival: 51 vs. 96 months, p = 0.019). Conclusions: The results of this retrospective study suggested that KL-6 and IL-6 could be used as predictors of short-term disease progression. In addition, high levels of KL-6 could be used as a predictor of mortality. Additional studies involving a larger patient cohort are warranted.

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