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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The authors will provide the raw data supporting the conclusions of this article without any reservation.
References
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
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
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
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
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
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
Frampton JE (2015) Febuxostat: a review of its use in the treatment of hyperuricaemia in patients with gout. Drugs 75(4):427–438
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
Seth R, Kydd AS, Buchbinder R, Bombardier C (2014) Edwards CJ (2014) Allopurinol for chronic gout. Cochrane Database Syst Rev 10:Cd006077
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
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
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
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
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
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
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
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
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
Robinson PC, Dalbeth N (2015) Advances in pharmacotherapy for the treatment of gout. Expert Opin Pharmacother 16(4):533–546
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
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
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
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
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
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
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
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
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
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
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
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
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
Terkeltaub R (2010) Update on gout: new therapeutic strategies and options. Nat Rev Rheumatol 6(1):30–38
Dalbeth N, Gosling AL, Gaffo A, Abhishek A (2021) Gout Lancet 397(10287):1843–1855
Dalbeth N, Merriman TR, Stamp LK (2016) Gout Lancet 388(10055):2039–2052
Perez-Ruiz F (2009) Treating to target: a strategy to cure gout. Rheumatol (Oxford) 48(Suppl 2):ii9–ii14
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
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
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
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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(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.
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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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DOI: https://doi.org/10.1007/s10067-024-06933-4