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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

  • Zepeng Mu
  • Wei Wang
  • Jing Wang
  • Wenshan Lv
  • Ying Chen
  • Fang Wang
  • Xiaolong Yu
  • Yangang Wang
  • Bingfei Cheng
  • Zhongchao WangEmail author
Original Article
  • 11 Downloads

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.

Keywords

Gout Predictors Treatment outcomes Urate-lowering therapy 

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

Notes

Acknowledgments

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

Authors’ 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.

Compliance with ethical standards

Disclosures

None.

Ethical standards

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.

Supplementary material

10067_2019_4737_MOESM1_ESM.xlsx (12 kb)
ESM 1 (XLSX 12 kb)

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Copyright information

© International League of Associations for Rheumatology (ILAR) 2019

Authors and Affiliations

  • Zepeng Mu
    • 1
  • Wei Wang
    • 1
  • Jing Wang
    • 1
  • Wenshan Lv
    • 1
  • Ying Chen
    • 1
  • Fang Wang
    • 1
  • Xiaolong Yu
    • 1
  • Yangang Wang
    • 1
  • Bingfei Cheng
    • 1
  • Zhongchao Wang
    • 1
    • 2
    Email author
  1. 1.The Affiliated Hospital of Qingdao UniversityQingdaoChina
  2. 2.Department of EndocrinologyThe Affiliated Hospital of Qingdao UniversityQingdaoChina

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