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Comparison of the efficacy and safety of benzbromarone and febuxostat in gout and hyperuricemia: a systematic review and meta-analysis

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Abstract

Objective

Urate-lowering therapy (ULT) is widely recognized as the primary treatment for hyperuricemia and gout. Xanthine oxidase inhibitors (XOI), particularly febuxostat, have gained popularity as a frontline approach. However, the divergent efficacy and safety between febuxostat and the traditional ULT drug, benzbromarone, remain poorly understood. This knowledge gap necessitates a comprehensive analysis and evidence update to guide drug selection for physicians and patients.

Method

We conducted a systematic analysis by extracting relevant clinical studies from four medical literature databases. Forest plots, funnel plots, sensitivity analysis, Egger’s test, and subgroup analysis were utilized to compare relevant indicators.

Results

The advantages and disadvantages of the two drugs were evaluated based on various indicators such as serum uric acid (SUA), triglyceride (TG), urinary uric acid (UUA), white blood cell count (WBC), total cholesterol (TC), blood urea nitrogen (BUN), alanine aminotransferase (ALT), aspartate aminotransferase (AST), estimated glomerular filtration rate (eGFR), and serum creatinine (SC). Benzbromarone demonstrated better efficacy in rapidly reducing SUA levels and inhibiting inflammation for hyperuricemia and gout patients. Febuxostat was slightly less effective in lowering SUA, but there was no significant difference in its impact on liver and kidney function after long-term use.

Conclusion

This study highlights the superiority of benzbromarone in rapidly reducing SUA and inhibiting inflammation. Febuxostat shows comparable effects on liver and kidney function after long-term use. These findings provide valuable insights for clinicians and patients in drug selection.

Key Points

• Benzbromarone stands out as a highly effective treatment for hyperuricemia and gout, offering rapid reduction of serum uric acid levels and potent anti-inflammatory effects.

• When it comes to long-term use, febuxostat demonstrates comparable effects on liver and kidney function. This provides reassurance for patients who require extended treatment duration.

• Moreover, our study goes beyond previous research by presenting a more comprehensive and detailed analysis.

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Data availability

The authors will provide the raw data supporting the conclusions of this article without any reservation.

References

  1. McAdams DeMarco MA, Maynard JW, Baer AN, Gelber AC, Young JH, Alonso A et al (2012) Diuretic use, increased serum urate levels, and risk of incident gout in a population-based study of adults with hypertension: the Atherosclerosis Risk in Communities cohort study. Arthritis Rheum 64(1):121–129

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Liu X, Zhai T, Ma R, Luo C, Wang H, Liu L (2018) Effects of uric acid-lowering therapy on the progression of chronic kidney disease: a systematic review and meta-analysis. Ren Fail 40(1):289–297

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Shoji A, Yamanaka H, Kamatani N (2004) A retrospective study of the relationship between serum urate level and recurrent attacks of gouty arthritis: evidence for reduction of recurrent gouty arthritis with antihyperuricemic therapy. Arthritis Rheum 51(3):321–325

    Article  CAS  PubMed  Google Scholar 

  4. FitzGerald JD, Dalbeth N, Mikuls T, Brignardello-Petersen R, Guyatt G, Abeles AM et al (2020) 2020 American College of Rheumatology guideline for the management of gout. Arthritis Rheumatol 72(6):879–895

    Article  PubMed  Google Scholar 

  5. Richette P, Doherty M, Pascual E, Barskova V, Becce F, Castañeda-Sanabria J et al (2017) 2016 updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis 76(1):29–42

    Article  CAS  PubMed  Google Scholar 

  6. Azevedo VF, Kos IA, Vargas-Santos AB, da Rocha CastelarPinheiro G, Dos Santos Paiva E (2019) Benzbromarone in the treatment of gout. Adv Rheumatol 59(1):37

    Article  PubMed  Google Scholar 

  7. Frampton JE (2015) Febuxostat: a review of its use in the treatment of hyperuricaemia in patients with gout. Drugs 75(4):427–438

    Article  CAS  PubMed  Google Scholar 

  8. Kunishima C, Inoue I, Oikawa T, Nakajima H, Komoda T, Katayama S (2007) Activating effect of benzbromarone, a uricosuric drug, on peroxisome proliferator-activated receptors. PPAR Res 2007:36092

    Article  PubMed  PubMed Central  Google Scholar 

  9. Seth R, Kydd AS, Buchbinder R, Bombardier C (2014) Edwards CJ (2014) Allopurinol for chronic gout. Cochrane Database Syst Rev 10:Cd006077

    Google Scholar 

  10. Wagayama H, Shiraki K, Sugimoto K, Fujikawa K, Shimizu A, Takase K et al (2000) Fatal fulminant hepatic failure associated with benzbromarone. J Hepatol 32(5):874

    Article  CAS  PubMed  Google Scholar 

  11. Kaufmann P, Török M, Hänni A, Roberts P, Gasser R, Krähenbühl S (2005) Mechanisms of benzarone and benzbromarone-induced hepatic toxicity. Hepatology 41(4):925–935

    Article  CAS  PubMed  Google Scholar 

  12. Fan M, Liu J, Zhao B, Wu X, Li X, Gu J et al (2021) Comparison of efficacy and safety of urate-lowering therapies for hyperuricemic patients with gout: a meta-analysis of randomized, controlled trials. Clin Rheumatol 40(2):683–692

    Article  PubMed  Google Scholar 

  13. Yu H, Liu X, Song Y, Cheng J, Bao H, Qin L et al (2018) Safety and efficacy of benzbromarone and febuxostat in hyperuricemia patients with chronic kidney disease: a prospective pilot study. Clin Exp Nephrol 22(6):1324–1330

    Article  CAS  PubMed  Google Scholar 

  14. Nakata T, Ikeda S, Koga S, Yonekura T, Tsuneto A, Doi Y et al (2020) Randomized, open-label, cross-over comparison of the effects of benzbromarone and febuxostat on endothelial function in patients with hyperuricemia. Int Heart J 61(5):984–92

    Article  CAS  PubMed  Google Scholar 

  15. Yan F, Xue X, Lu J, Dalbeth N, Qi H, Yu Q et al (2022) Superiority of low-dose benzbromarone to low-dose febuxostat in a prospective, randomized comparative effectiveness trial in gout patients with renal uric acid underexcretion. Arthritis Rheumatol 74(12):2015–2023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Sapankaew T, Thadanipon K, Ruenroengbun N, Chaiyakittisopon K, Ingsathit A, Numthavaj P et al (2022) Efficacy and safety of urate-lowering agents in asymptomatic hyperuricemia: systematic review and network meta-analysis of randomized controlled trials. BMC Nephrol 23(1):223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Lee YH, Song GG (2022) Comparative efficacy and safety of dotinurad, febuxostat, and benzbromarone in hyperuricemic patients with or without gout: a network meta-analysis of randomized controlled trials. Int J Clin Pharmacol Ther 60(3):159–166

    Article  CAS  PubMed  Google Scholar 

  18. Dalbeth N, Doyle AJ, Billington K, Gamble GD, Tan P, Latto K et al (2022) Intensive serum urate lowering with oral urate-lowering therapy for erosive gout: a randomized double-blind controlled trial. Arthritis Rheumatol 74(6):1059–1069

    Article  CAS  PubMed  Google Scholar 

  19. Robinson PC, Dalbeth N (2015) Advances in pharmacotherapy for the treatment of gout. Expert Opin Pharmacother 16(4):533–546

    Article  CAS  PubMed  Google Scholar 

  20. Chou HW, Chiu HT, Tsai CW, Ting IW, Yeh HC, Huang HC et al (2018) Comparative effectiveness of allopurinol, febuxostat and benzbromarone on renal function in chronic kidney disease patients with hyperuricemia: a 13-year inception cohort study. Nephrol Dial Transplant 33(9):1620–1627

    CAS  PubMed  Google Scholar 

  21. Liang N, Sun M, Sun R, Xu T, Cui L, Wang C et al (2019) Baseline urate level and renal function predict outcomes of urate-lowering therapy using low doses of febuxostat and benzbromarone: a prospective, randomized controlled study in a Chinese primary gout cohort. Arthritis Res Ther 21(1):200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD et al (2021) The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 372:n71

    Article  PubMed  PubMed Central  Google Scholar 

  23. Austin PC, White IR, Lee DS, van Buuren S (2021) Missing data in clinical research: a tutorial on multiple imputation. Can J Cardiol 37(9):1322–1331

    Article  PubMed  Google Scholar 

  24. Wells G, Shea B, O’Connell D, Robertson J, Peterson J, Welch V et al (2011) The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses (2011). Ottawa Hospital Research Institute, Ottawa

    Google Scholar 

  25. Howick J, Chalmers I, Glasziou P, Greenhalgh T, Heneghan C, Liberati A (2011) Explanation of the 2011 Oxford Centre for Evidence-Based Medicine (OCEBM) levels of evidence (background document). OCEBM Web site. https://www.cebm.ox.ac.uk/resources/levels-of-evidence/explanation-of-the-2011-ocebm-levels-of-evidence

  26. Luo D, Wan X, Liu J, Tong T (2018) Optimally estimating the sample mean from the sample size, median, mid-range, and/or mid-quartile range. Stat Methods Med Res 27(6):1785–1805

    Article  PubMed  Google Scholar 

  27. Kim SR, Kim K, Lee SA, Kwon SO, Lee JK, Keum N et al (2019) Effect of red, processed, and white meat consumption on the risk of gastric cancer: an overall and dose-response meta-analysis. Nutrients 11(4):826. https://doi.org/10.3390/nu11040826. PMID: 30979076; PMCID: PMC65

  28. Ohta Y, Ishizuka A, Arima H, Hayashi S, Iwashima Y, Kishida M et al (2017) Effective uric acid-lowering treatment for hypertensive patients with hyperuricemia. Hypertens Res 40(3):259–263

    Article  CAS  PubMed  Google Scholar 

  29. Cumpston M, Li T, Page MJ, Chandler J, Welch VA, Higgins JP et al (2019) Updated guidance for trusted systematic reviews: a new edition of the Cochrane Handbook for Systematic Reviews of Interventions. Cochrane Database Syst Rev 10(10): Ed000142

  30. Wu J, Zhang YP, Qu Y, Jie LG, Deng JX, Yu QH (2019) Efficacy of uric acid-lowering therapy on hypercholesterolemia and hypertriglyceridemia in gouty patients. Int J Rheum Dis 22(8):1445–1451

    Article  CAS  PubMed  Google Scholar 

  31. Liu D, Zhou B, Li Z, Zhang Z, Dai X, Ji Z et al (2022) Effectiveness of benzbromarone versus febuxostat in gouty patients: a retrospective study. Clin Rheumatol 41(7):2121–2128

    Article  CAS  PubMed  Google Scholar 

  32. Nishino M, Egami Y, Nakamura H, Ukita K, Kawamura A, Matsuhiro Y et al (2022) Prospective randomized comparison of effect on coronary endothelial and renal function between febuxostat and benzbromarone in hyperuricemic patients with coronary artery disease: EFEF study. Health Sci Rep 5(2):e563

    Article  PubMed  PubMed Central  Google Scholar 

  33. Terkeltaub R (2010) Update on gout: new therapeutic strategies and options. Nat Rev Rheumatol 6(1):30–38

    Article  CAS  PubMed  Google Scholar 

  34. Dalbeth N, Gosling AL, Gaffo A, Abhishek A (2021) Gout Lancet 397(10287):1843–1855

    Article  CAS  PubMed  Google Scholar 

  35. Dalbeth N, Merriman TR, Stamp LK (2016) Gout Lancet 388(10055):2039–2052

    Article  CAS  PubMed  Google Scholar 

  36. Perez-Ruiz F (2009) Treating to target: a strategy to cure gout. Rheumatol (Oxford) 48(Suppl 2):ii9–ii14

    Article  CAS  Google Scholar 

  37. Li W, Wang Y, Ouyang S, Li M, Liu R, Zhang Y et al (2022) Association between serum uric acid level and carotid atherosclerosis and metabolic syndrome in patients with type 2 diabetes mellitus. Front Endocrinol (Lausanne) 13:890305

    Article  PubMed  Google Scholar 

  38. Banach M, Duell PB, Gotto AM Jr, Laufs U, Leiter LA, Mancini GBJ et al (2020) Association of bempedoic acid administration with atherogenic lipid levels in phase 3 randomized clinical trials of patients with hypercholesterolemia. JAMA Cardiol 5(10):1124–1135

    Article  PubMed  Google Scholar 

  39. Ali N, Rahman S, Islam S, Haque T, Molla NH, Sumon AH et al (2019) The relationship between serum uric acid and lipid profile in Bangladeshi adults. BMC Cardiovasc Disord 19(1):42

    Article  PubMed  PubMed Central  Google Scholar 

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Funding

This work was financially supported by the National Natural Science Foundation of China grants (82074081, 82374104), Knowledge Innovation Program of Wuhan-Basic Research (2022020801010404), and “the Fundamental Research Funds for the Central Universities” South-Central Minzu University (CZZ23009). Also, this study was funded by the Department of Cardiology, Union Hospital, Tongji Medical University, Huazhong University of Science and Technology (82170326).

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Authors and Affiliations

  1. School of Pharmaceutical Sciences, South-Central Minzu University, No. 182 Minzu Avenue, Wuhan, 430074, Hubei, China

    Fan Wu & Lvyi Chen

  2. Department of Cardiology, Union Hospital, Tongji Medical University, Huazhong University of Science and Technology, No. 1277, Jiefang Avenue, Wuhan, 430022, Hubei, China

    Yimei Du

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  1. Fan Wu
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Contributions

(I) Conception and design: FW and LYC. (II) Administrative support: YMD and LYC. (III) Provision of study materials or patients: FW and YMD. (IV) Collection and assembly of data: FW and LYC. (V) Data analysis and interpretation: FW and LYC and YMD. (VI) Manuscript writing: FW and LYC and YMD. All authors contributed to the article and approved the submitted version.

Corresponding authors

Correspondence to Lvyi Chen or Yimei Du.

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Wu, F., Chen, L. & Du, Y. Comparison of the efficacy and safety of benzbromarone and febuxostat in gout and hyperuricemia: a systematic review and meta-analysis. Clin Rheumatol 43, 1745–1754 (2024). https://doi.org/10.1007/s10067-024-06933-4

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