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

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Abstract

Introduction

Clinical guidelines have recommended a target of serum uric acid (SUA) level below 6.0 mg/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.

Methods

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 ≥ 8.0 mg/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 6.0 mg/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.

Results

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.

Conclusion

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.

Trial registration

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.

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Abbreviations

ACR:

American College of Rheumatology

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

BMI:

Body mass index

BUN:

Blood urea nitrogen

Cr:

Creatinine

DBP:

Diastolic blood pressure

EULAR:

European League Against Rheumatism

FBG:

Fasting blood glucose

LDL:

Low density lipoprotein

OR:

Odds ratio

SBP:

Systolic blood pressure

SUA:

Serum uric acid

T2DM:

Type 2 diabetes mellitus

TBIL:

Total bilirubin

TC:

Total cholesterol

TG:

Triglyceride

ULT:

Urate-lowering therapy

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Acknowledgments

We thank Dr. Robin Wang for advice regarding statistical analysis of data.

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Authors and Affiliations

  1. The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003, China

    Zepeng Mu, Wei Wang, Jing Wang, Wenshan Lv, Ying Chen, Fang Wang, Xiaolong Yu, Yangang Wang, Bingfei Cheng & Zhongchao Wang

  2. Department of Endocrinology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003, China

    Zhongchao Wang

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  1. Zepeng Mu
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  2. Wei Wang
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Contributions

All authors contributed to the study conception and design, data collection, analysis of the data, interpretation of the results, and drafting of the manuscript. All authors revised the manuscript and approved the final version.

Corresponding author

Correspondence to Zhongchao Wang.

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This clinical trial conformed to principles of the Declaration of Helsinki and the Good Clinical Practice of China and was approved by the Drug Clinical Trial Ethics Committee, Shandong Provincial Hospital. All participants provided written informed consent.

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Mu, Z., Wang, W., Wang, J. et al. Predictors of poor response to urate-lowering therapy in patients with gout and hyperuricemia: a post-hoc analysis of a multicenter randomized trial. Clin Rheumatol 38, 3511–3519 (2019). https://doi.org/10.1007/s10067-019-04737-5

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