Predictors of poor response to urate-lowering therapy in patients with gout and hyperuricemia: a post-hoc analysis of a multicenter randomized trial

Abstract

Clinical guidelines have recommended a target of serum uric acid (SUA) level below 6.0mg/dL for the urate-lowering therapy (ULT) of gout patients, but there are still a high proportion of patients failing to achieve the therapeutic target above. This study aimed to identify possible predictors of poor response to ULT in gout patients. We performed a post-hoc analysis of a multicenter randomized double-blind trial which assessed the efficacy of febuxostat in patients with hyperuricemia (serum urate level ≥ 8.0mg/dL) and gout. Demographic characters and baseline data including SUA levels were collected. Poor response to ULT was defined as average SUA after ULT was more than 6.0mg/dL. Factors associated with poor response to ULT in gout patients were analyzed, and multivariate logistic regression analysis was also carried out to find out those independent predictors. A total of 370 patients were enrolled in this post-hoc analysis. Compared with those with good response to ULT, patients with poor response to ULT had younger age (P < 0.001), higher proportion of obesity (P = 0.003), higher proportion of statins use (P = 0.019), higher body mass index (BMI) (P < 0.001), higher baseline SUA (P < 0.001), higher proportion of males (P = 0.001), higher alanine transaminase (P < 0.001), higher aspartate transaminase (P = 0.017), higher total cholesterol (P = 0.005), higher triglyceride (P = 0.042), and higher low density lipoprotein (P = 0.037). Multivariate logistic regression analysis showed that younger age (odds ratio (OR) = 0.965, 95% CI 0.943-0.987, P = 0.002), higher BMI (OR = 1.133, 95% CI 1.049-1.224, P = 0.001), higher baseline SUA (OR = 1.006, 95% CI 1.002-1.009, P = 0.001), and no application of febuxostat therapy (OR = 0.41, 95% CI 0.25-0.68, P < 0.001) were independent predictors of poor response to ULT in patients with gout. In patients with gout and hyperuricemia, younger age, higher BMI, and higher baseline SUA are predictors of poor response to ULT. These findings could help physicians better identify patients who may fail in ULT and give individualized treatment precisely. The trial was registered at chinadrugtrials.org.cn in 2012 (CTR20130172).Key Points• A post-hoc analysis of a multicenter randomized double-blind trial which assessed the efficacy of febuxostat in patients with hyperuricemia and gout was performed.• Multivariate logistic regression analysis showed that younger age, higher BMI, and higher baseline SUA are predictors of poor response to urate-lowering therapy.