The clinical efficacy of urate-lowering therapy in acute gout: a meta-analysis of randomized controlled trials



Gout is a common chronic disease with a high recurrence rate. To date, the debate continues about the best time for using urate lowering therapy (ULT) during an acute gout attack.


This updated meta-analysis is designed to assess the clinical efficacy of ULT in the management of acute exacerbations of gout. Through the results, we hope to determine whether uric acid lowering agents should be used to manage acute exacerbations of gout.


A comprehensive search of six databases without language restrictions includes PubMed, Cochrane Library, Web of Science, EMBASE, CNKI, and WanFang data. The literature used was published before October 2019. Six randomized controlled trials (RCTs) with 557 patients met the inclusion criteria. Standardized mean difference (SMD), weighted mean difference (WMD), risk ratio (RR), and 95% confidence interval (CI) were used for estimating the clinical efficacy of ULT in acute gout.


Data results showed no statistical difference in the pain visual analogue score (VAS) by day 3 (weighted mean difference (WMD), 0.06; 95% CI, − 0.13 to 0.25; I2 0%; P = 0.55), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) between the group using uric acid lowering agents and the group that was not using such agents. Moreover, the patients using ULT agents had lower serum uric acid level (standardized mean difference (SMD), − 0.73; 95% CI, −0.92 to −0.54; I2 23%; P < 0.00001) and showed better adherence to medication (risk ratio (RR), 1.40; 95% CI, 1.18 to 1.65; I2 0%; P < 0.0001) as compared with the patients not that were not using such agents. However, there was no substantial difference in the recurrence rate of acute gout attacks (RR, 0.84; 95% CI, 0.59 to 1.19; I2 0%; P = 0.33).The evidence for this is, however, very moderate.


Our finding shows that it is beneficial in many aspects to use uric-acid-lowering drugs at the initial stage of an acute gout attack. However, larger sample size studies are still needed to prove our results.

Trial registration

Registration number: PROSPERO (CRD42020153924).

Key Points
• This is a first meta-analysis about the clinical efficacy of urate-lowering therapy (ULT) in acute gout without language restrictions.
• ULT in acute gout may not aggravate the pain (WMD, 0.06; 95% CI, − 0.13 to 0.25).
• ULT at the initial stage of an acute gout attack can reduce serum uric acid level (SMD, −0.73; 95% CI, − 0.92 to − 0.54) and improve medication compliance in patients (RR, 1.40; 95% CI, 1.18 to 1.65).
• ULT in acute gout is not associated with the risk of gout flares (RR, 0.84; 95% CI, 0.59 to 1.19).

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7


  1. 1.

    Chen-Xu M, Yokose C, Rai SK, Pillinger MH, Choi HK (2019) Contemporary prevalence of gout and hyperuricemia in the United States and decadal trends: the National Health and nutrition examination survey, 2007-2016. Arthritis Rheumatol 71(6):991–999.

    Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Kuo CF, Grainge MJ, Zhang W, Doherty M (2015) Global epidemiology of gout: prevalence, incidence and risk factors. Nat Rev Rheumatol 11(11):649–662.

    Article  PubMed  Google Scholar 

  3. 3.

    Xiong YF, Zhao DB (2018) Interpretation of management of acute and recurrent gout:a clinical practice guideline from the American College of Physicians. Chin Gen Pract 21(14):1645–1647.

    Article  Google Scholar 

  4. 4.

    Richette P, Doherty M, Pascual E, Barskova V, Becce F, Castañeda-Sanabria J, Coyfish M, Guillo S, Jansen TL, Janssens H, Lioté F, Mallen C, Nuki G, Perez-Ruiz F, Pimentao J, Punzi L, Pywell T, So A, Tausche AK, Uhlig T, Zavada J, Zhang W, Tubach F, Bardin T (2017) 2016 updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis 76(1):29–42.

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Eminaga F, Le-Carratt J, Jones A, Abhishek A (2016) Does the initiation of urate-lowering treatment during an acute gout attack prolong the current episode and precipitate recurrent attacks: a systematic literature review. Rheumatol Int 36(12):1747–1752.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Michelle H, Alison C, Stewart C, Graham D, Michael D, Harry F et al (2017) The British Society for Rheumatology Guideline for the Management of Gout. Rheumatology 56(7):1056–1059.

    CAS  Article  Google Scholar 

  7. 7.

    Feng X, Li Y, Gao W (2015) Significance of the initiation time of urate-lowering therapy in gout patients: a retrospective research. Joint Bone Spine 82(6):428–431.

    Article  PubMed  Google Scholar 

  8. 8.

    Janssen C, Oude Voshaar M, Ten K, Vonkeman H, Van de L (2019) Prognostic factors associated with early gout flare recurrence in patients initiating urate-lowering therapy during an acute gout flare. Clin Rheumatol 38(8):2233–2239.

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Hill EM, Sky K, Sit M, Collamer A, Higgs J (2015) Does starting allopurinol prolong acute treated gout? A randomized clinical trial. J Clin Rheumatol 21(3):120–125.

    Article  PubMed  Google Scholar 

  10. 10.

    Taylor TH, Mecchella JN, Larson RJ, Kerin KD, MacKenzie TA (2012) Initiation of allopurinol at first medical contact for acute attacks of gout: a randomized clinical trial. Am J Med 125(11):1126–1134.

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Zhang ZM, Huang QQ, Qi ZY, Zhao ZW, Wu KY, Cheng YY et al (2019) Effect of initial hypouric acid therapy for acute gout on clinical efficacy and medication compliance. Rheumatism Arthritis 8(4):24–27.

    Article  Google Scholar 

  12. 12.

    Zhang XF, Zhong Q (2015) Effect of urate-lowering therapy on recurrence and serum uric acid in acute primary gout. Pract Clin J Integr Tradit Chin West Med 15(3):54–55.

    CAS  Article  Google Scholar 

  13. 13.

    Wang XF, Zhang JZ, Wang T, Li WJ, Liu AH, Sun RX (2019) Effects of urate-lowering therapy on inflammatory responses, gout flares occurrances, and the achieved target rate of serum uric acid in acute gout. Chin J Endocrinol Metab 35(6):486–490.

    CAS  Article  Google Scholar 

  14. 14.

    Ye SK, Li XY, Ren X, Chen HY, Niu J (2019) Application of febuxostat in patients with acute gouty arthritis. Mil Med J South China 33(5):307–311.

    Article  Google Scholar 

  15. 15.

    Wan X, Wang WQ, Liu JM, Tong TJ (2014) Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol 14:135.

    Article  PubMed  PubMed Central  Google Scholar 

  16. 16.

    Luo DH, Wan X, Liu JM, Tong TJ (2018) Optimally estimating the sample mean from the sample size, median, mid-range, and/or mid-quartile range. Stat Methods Med Res 27(6):1785–1850.

    Article  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Qaseem A, McLean RM, Starkey M, Forciea MA (2017) Diagnosis of acute gout: a clinical practice guideline from the American College of Physicians. Ann Intern Med 166(1):52–57.

    Article  PubMed  Google Scholar 

  18. 18.

    Landis RC, Haskard DO (2001) Pathogenesis of crystal-induced inflammation. Curr Rheumatol Rep 3(1):36–41.

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Shenkar R, Abraham E (1999) Mechanisms of lung neutrophil activation after hemorrhage or endotoxemia: roles of reactive oxygen intermediates, NF-kappa B, and cyclic AMP response element binding protein. J Immunol 163(2):954–962

    CAS  PubMed  Google Scholar 

  20. 20.

    Vranken L, Boonen A, Spaetgens B (2019) Outcome measurement in acute gout: about constructs, perspectives, scales and timing. Rheumatology (Oxford) 58(11):1891–1893.

    Article  Google Scholar 

  21. 21.

    Akira S, Hisashi Y, Naoyuki K (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.

    CAS  Article  Google Scholar 

  22. 22.

    Li-Yu J, Clayburne G, Sieck M, Beutler A, Rull M, Eisner E et al (2001) Treatment of chronic gout. Can we determine when urate stores are depleted enough to prevent attacks of gout? J Rheumatol 28(3):577–580

    CAS  PubMed  Google Scholar 

  23. 23.

    Primatesta P, Plana E, Rothenbacher D (2011) Gout treatment and comorbidities: a retrospective cohort study in a large US managed care population. BMC Musculoskelet Disord 12:103.

    Article  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Aung T, Myung G, FitzGerald JD (2017) Treatment approaches and adherence to urate-lowering therapy for patients with gout. Patient Prefer Adher 11:795–800.

    Article  Google Scholar 

Download references


We would like to acknowledge the grants from the 01 National Science and Technology Major Project (No. 2018ZX01031201).


This work was supported by the grants from the 01 National Science and Technology Major Project (No. 2018ZX01031201).

Author information



Corresponding authors

Correspondence to Dongsheng Wang or Qiuyan Li.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants performed by any of the authors.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Zhang, X., Tang, Y., Wang, M. et al. The clinical efficacy of urate-lowering therapy in acute gout: a meta-analysis of randomized controlled trials. Clin Rheumatol 40, 701–710 (2021).

Download citation


  • Acute gout
  • Clinical efficacy
  • Meta-analysis
  • Urate-lowering therapy