Systemic inflammation in gout and the impact of treat-to-target urate-lowering therapy

OBJECTIVES: We tested the hypotheses that individuals with gout would have distinct circulating inflammatory biomarker patterns compared with non-gout controls and that these differences would be attenuated with highly-effective urate-lowering therapy (ULT). METHODS: This case-control and longitudinal cohort study utilized longitudinal serum samples from a subset of participants from the STOP Gout study and non-gout controls from an institutional biobank at a single time point. Twenty pre-selected inflammatory and cardiometabolic biomarkers were measured and varimax-rotated principal component analysis (PCA) performed. An inflammatory score was generated using standardized biomarker values representing PCs associated with gout and compared between controls and gout patients, and among gout patients over time. A generalized estimating equation was used to assess interactions between clinical factors and change in inflammatory score over time. RESULTS: Five PCs statistically differed in gout (n = 278) at baseline vs. controls (n = 275) after accounting for covariates. Mean inflammatory scores of gout cases at all three time points were increased vs. controls (p < 0.001). There was a decrease in inflammatory scores at both 24- (p = 0.01) and 48-weeks (p < 0.001) vs. baseline among gout cases. Higher baseline score and time were associated with reductions in inflammatory score, whereas hypertension and higher baseline serum urate were associated with an increased inflammatory score. CONCLUSION: Gout is characterized by distinct patterns of circulating inflammatory biomarkers and these appear to change over time with treat-to-target ULT to approximate controls. This study supports the importance of treat-to-target ULT in gout management not only for flare prevention, but also to mitigate systemic inflammation.