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Prevention of recurrent gout: Pharmacologic urate-lowering therapy and treatment of tophi

Michael A Becker, MD
Section Editor
Nicola Dalbeth, MBChB, MD, FRACP
Deputy Editor
Paul L Romain, MD


Gout is monosodium urate crystal deposition disease; in the absence of urate saturation of extracellular fluids (reflected by hyperuricemia: serum urate levels >6.8 mg/dL [405 micromol/L]) and of urate crystal deposition and inflammatory responses to crystal deposition, the symptoms and signs of gout do not occur. In addition, there is no evidence that serum urate reduction to levels that remain above the limit of solubility carries with it clinical benefits equivalent to those achievable at sub-saturating levels. Thus, gout can be regarded as a “threshold” disease in which the long-term goal of therapy to prevent recurrent gout and reverse prior signs of the disease is to achieve and maintain sub-saturating serum urate concentrations.

Management for the prevention of recurrent episodes of acute gout and damage to joints and other tissues from urate crystal deposition includes drug therapy as well as lifestyle modification and other strategies for risk reduction. Long-term success in maintaining sub-saturating urate levels is attended by clinical benefits that include cessation of acute gout flares, resolution of tophi, and improvement in patient physical function and health-related quality of life. However, resolution of the urate crystal burden may require many months to several years to attain, even after sub-saturating urate levels are achieved either by lifestyle modifications (risk reduction) and/or with oral urate-lowering agents. During this period of crystal dissolution, a risk for acute flare remains and is the primary basis for gout flare prophylaxis with antiinflammatory agents.

The prevention of recurrent gout and of disease progression by use of urate-lowering drugs and the treatment of tophi will be reviewed here, as will antiinflammatory prophylaxis of acute gouty arthritis during initiation of antihyperuricemic therapy. The prevention of recurrent gout and disease progression by use of nonpharmacologic lifestyle modifications for urate lowering and by risk reduction involving drug choices for management of comorbid diseases (eg, hypertension), the clinical manifestations and diagnosis of gout, the treatment of episodes of acute gouty arthritis, and issues related to asymptomatic hyperuricemia are discussed separately. (See "Prevention of recurrent gout: Lifestyle modification and other strategies for risk reduction" and "Clinical manifestations and diagnosis of gout" and "Treatment of acute gout" and "Asymptomatic hyperuricemia".)


In most patients with gouty arthritis, the disease can be successfully managed by achieving and maintaining a sub-saturating target serum urate level with lifestyle modification/risk reduction strategies combined, as is often necessary, with pharmacologic therapy. Pharmacologic urate-lowering measures are usually required in patients with tophaceous gout, although, in a few patients with complications due to tophaceous disease, surgical intervention may be an adjunct to medical management. Treatment may be more challenging in patients with compromised renal function and large tophaceous deposits.

Upon resolution of an acute gouty attack, the patient is said to have entered an intercritical (between attacks) period (see "Clinical manifestations and diagnosis of gout", section on 'Intercritical gout and recurrent gouty arthritis'); during this period, the following preventive issues should be addressed:

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Literature review current through: Nov 2017. | This topic last updated: May 18, 2017.
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  1. Choi HK, Atkinson K, Karlson EW, et al. Alcohol intake and risk of incident gout in men: a prospective study. Lancet 2004; 363:1277.
  2. Choi HK, Liu S, Curhan G. Intake of purine-rich foods, protein, and dairy products and relationship to serum levels of uric acid: the Third National Health and Nutrition Examination Survey. Arthritis Rheum 2005; 52:283.
  3. Choi HK, Atkinson K, Karlson EW, et al. Purine-rich foods, dairy and protein intake, and the risk of gout in men. N Engl J Med 2004; 350:1093.
  4. Becker MA, Jolly M. Hyperuricemia and associated diseases. Rheum Dis Clin North Am 2006; 32:275.
  5. Whelton A, Macdonald PA, Zhao L, et al. Renal function in gout: long-term treatment effects of febuxostat. J Clin Rheumatol 2011; 17:7.
  6. Goicoechea M, de Vinuesa SG, Verdalles U, et al. Effect of allopurinol in chronic kidney disease progression and cardiovascular risk. Clin J Am Soc Nephrol 2010; 5:1388.
  7. Becker MA, Jolly M. Clinical gout and the pathogenesis of hyperuricemia. In: Arthritis and Allied Conditions, 15th Edition, Koopman WJ, Moreland LW (Eds), Lippincott, Williams & Wilkins, Philadelphia 2005. p.2303.
  8. Zhang W, Doherty M, Bardin T, et al. EULAR evidence based recommendations for gout. Part II: Management. Report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis 2006; 65:1312.
  9. Wallace SL, Singer JZ. Therapy in gout. Rheum Dis Clin North Am 1988; 14:441.
  10. Shoji A, Yamanaka H, Kamatani N. 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 2004; 51:321.
  11. Perez-Ruiz F, Calabozo M, Pijoan JI, et al. Effect of urate-lowering therapy on the velocity of size reduction of tophi in chronic gout. Arthritis Rheum 2002; 47:356.
  12. Yamanaka H, Togashi R, Hakoda M, et al. Optimal range of serum urate concentrations to minimize risk of gouty attacks during anti-hyperuricemic treatment. Adv Exp Med Biol 1998; 431:13.
  13. Terkeltaub RA. Clinical practice. Gout. N Engl J Med 2003; 349:1647.
  14. Chen LX, Schumacher HR. Gout: can we create an evidence-based systematic approach to diagnosis and management? Best Pract Res Clin Rheumatol 2006; 20:673.
  15. Khanna D, Fitzgerald JD, Khanna PP, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res (Hoboken) 2012; 64:1431.
  16. Taylor TH, Mecchella JN, Larson RJ, et al. Initiation of allopurinol at first medical contact for acute attacks of gout: a randomized clinical trial. Am J Med 2012; 125:1126.
  17. Bull PW, Scott JT. Intermittent control of hyperuricemia in the treatment of gout. J Rheumatol 1989; 16:1246.
  18. Loebl WY, Scott JT. Withdrawal of allopurinol in patients with gout. Ann Rheum Dis 1974; 33:304.
  19. Gast LF. Withdrawal of longterm antihyperuricemic therapy in tophaceous gout. Clin Rheumatol 1987; 6:70.
  20. van Lieshout-Zuidema MF, Breedveld FC. Withdrawal of longterm antihyperuricemic therapy in tophaceous gout. J Rheumatol 1993; 20:1383.
  21. Perez-Ruiz F, Atxotegi J, Hernando I, et al. Using serum urate levels to determine the period free of gouty symptoms after withdrawal of long-term urate-lowering therapy: a prospective study. Arthritis Rheum 2006; 55:786.
  22. Sarawate CA, Patel PA, Schumacher HR, et al. Serum urate levels and gout flares: analysis from managed care data. J Clin Rheumatol 2006; 12:61.
  23. Riedel AA, Nelson M, Joseph-Ridge N, et al. Compliance with allopurinol therapy among managed care enrollees with gout: a retrospective analysis of administrative claims. J Rheumatol 2004; 31:1575.
  24. De Vera MA, Marcotte G, Rai S, et al. Medication adherence in gout: a systematic review. Arthritis Care Res (Hoboken) 2014; 66:1551.
  25. Jutkowitz E, Choi HK, Pizzi LT, Kuntz KM. Cost-effectiveness of allopurinol and febuxostat for the management of gout. Ann Intern Med 2014; 161:617.
  26. Jutkowitz E, Dubreuil M, Lu N, et al. The cost-effectiveness of HLA-B*5801 screening to guide initial urate-lowering therapy for gout in the United States. Semin Arthritis Rheum 2017; 46:594.
  27. Perez-Ruiz F, Inaki H, Herrero-Beites AM. Uricosuric therapy. In: Crystal-induced arthropathies. Gout, pseudogout and apatite-associated syndromes, Wortmann RL, Schumacher HR Jr, Becker MA, Ryan LM (Eds), Taylor & Francis, New York 2006. p.369.
  28. Perez-Ruiz F, Calabozo M, Fernandez-Lopez MJ, et al. Treatment of chronic gout in patients with renal function impairment: an open, randomized, actively controlled study. J Clin Rheumatol 1999; 5:49.
  29. Lee MH, Graham GG, Williams KM, Day RO. A benefit-risk assessment of benzbromarone in the treatment of gout. Was its withdrawal from the market in the best interest of patients? Drug Saf 2008; 31:643.
  30. Sarawate CA, Brewer KK, Yang W, et al. Gout medication treatment patterns and adherence to standards of care from a managed care perspective. Mayo Clin Proc 2006; 81:925.
  31. Rashid N, Coburn BW, Wu YL, et al. Modifiable factors associated with allopurinol adherence and outcomes among patients with gout in an integrated healthcare system. J Rheumatol 2015; 42:504.
  32. Becker MA, Fitz-Patrick D, Choi HK, et al. An open-label, 6-month study of allopurinol safety in gout: The LASSO study. Semin Arthritis Rheum 2015; 45:174.
  33. Becker MA, Schumacher HR Jr, Wortmann RL, et al. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N Engl J Med 2005; 353:2450.
  34. Becker MA, Schumacher HR, Espinoza LR, et al. The urate-lowering efficacy and safety of febuxostat in the treatment of the hyperuricemia of gout: the CONFIRMS trial. Arthritis Res Ther 2010; 12:R63.
  35. Schumacher HR Jr, Becker MA, Wortmann RL, et al. Effects of febuxostat versus allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout: a 28-week, phase III, randomized, double-blind, parallel-group trial. Arthritis Rheum 2008; 59:1540.
  36. Bhakta N, Saag KG, Adler S, et al. Lesinurad, a novel selective uric acid reabsorption inhibitor, in two phase III clinical trials: combination study of lesinurad in allorpurinol standard of care inadequate responders (CLEAR 1 and 2). Ann Rheum Dis 2015.
  37. Dalbeth N, Jones G, Terkeltaub R, et al. Lesinurad, a novel selective uric acid reabsorption inhibitor, in combination with febuxostat, in patients with tophaceous gout: the CRYSTAL phase III clinical trial. Ann Rheum Dis 2015.
  38. Hisatome I, Kosaka H, Ohtahara K, et al. Renal handling of urate in a patient with familial juvenile gouty nephropathy. Intern Med 1996; 35:564.
  39. Perez-Ruiz F, Sundy JS, Miner JN, et al. Lesinurad in combination with allopurinol: results of a phase 2, randomised, double-blind study in patients with gout with an inadequate response to allopurinol. Ann Rheum Dis 2016; 75:1074.
  40. Lockard O Jr, Harmon C, Nolph K, Irvin W. Allergic reaction to allopurinol with cross-reactivity to oxypurinol. Ann Intern Med 1976; 85:333.
  41. Perez-Ruiz F, Alonso-Ruiz A, Calabozo M, et al. Efficacy of allopurinol and benzbromarone for the control of hyperuricaemia. A pathogenic approach to the treatment of primary chronic gout. Ann Rheum Dis 1998; 57:545.
  42. Emmerson B. Hyperlipidaemia in hyperuricaemia and gout. Ann Rheum Dis 1998; 57:509.
  43. Stamp LK, Taylor WJ, Jones PB, et al. Starting dose is a risk factor for allopurinol hypersensitivity syndrome: a proposed safe starting dose of allopurinol. Arthritis Rheum 2012; 64:2529.
  44. Halevy S, Ghislain PD, Mockenhaupt M, et al. Allopurinol is the most common cause of Stevens-Johnson syndrome and toxic epidermal necrolysis in Europe and Israel. J Am Acad Dermatol 2008; 58:25.
  45. Hung SI, Chung WH, Liou LB, et al. HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proc Natl Acad Sci U S A 2005; 102:4134.
  46. Tassaneeyakul W, Jantararoungtong T, Chen P, et al. Strong association between HLA-B*5801 and allopurinol-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in a Thai population. Pharmacogenet Genomics 2009; 19:704.
  47. Cao ZH, Wei ZY, Zhu QY, et al. HLA-B*58:01 allele is associated with augmented risk for both mild and severe cutaneous adverse reactions induced by allopurinol in Han Chinese. Pharmacogenomics 2012; 13:1193.
  48. Hershfield MS, Callaghan JT, Tassaneeyakul W, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for human leukocyte antigen-B genotype and allopurinol dosing. Clin Pharmacol Ther 2013; 93:153.
  49. Zineh I, Mummaneni P, Lyndly J, et al. Allopurinol pharmacogenetics: assessment of potential clinical usefulness. Pharmacogenomics 2011; 12:1741.
  50. Chung WH, Chang WC, Stocker SL, et al. Insights into the poor prognosis of allopurinol-induced severe cutaneous adverse reactions: the impact of renal insufficiency, high plasma levels of oxypurinol and granulysin. Ann Rheum Dis 2015; 74:2157.
  51. Ko TM, Tsai CY, Chen SY, et al. Use of HLA-B*58:01 genotyping to prevent allopurinol induced severe cutaneous adverse reactions in Taiwan: national prospective cohort study. BMJ 2015; 351:h4848.
  52. Fam AG, Lewtas J, Stein J, Paton TW. Desensitization to allopurinol in patients with gout and cutaneous reactions. Am J Med 1992; 93:299.
  53. Fam AG, Paton TW, Chaiton A. Reinstitution of allopurinol therapy for gouty arthritis after cutaneous reactions. Can Med Assoc J 1980; 123:128.
  54. Webster E, Panush RS. Allopurinol hypersensitivity in a patient with severe, chronic, tophaceous gout. Arthritis Rheum 1985; 28:707.
  55. Kelsey SM, Struthers GR, Beswick T, Blake DR. Desensitisation to allopurinol. Ann Rheum Dis 1987; 46:84.
  56. Fam AG, Dunne SM, Iazzetta J, Paton TW. Efficacy and safety of desensitization to allopurinol following cutaneous reactions. Arthritis Rheum 2001; 44:231.
  57. Unsworth J, Blake DR, d'Assis Fonseca AE, Beswick DT. Desensitisation to allopurinol: a cautionary tale. Ann Rheum Dis 1987; 46:646.
  58. Hande KR, Noone RM, Stone WJ. Severe allopurinol toxicity. Description and guidelines for prevention in patients with renal insufficiency. Am J Med 1984; 76:47.
  59. Singer JZ, Wallace SL. The allopurinol hypersensitivity syndrome. Unnecessary morbidity and mortality. Arthritis Rheum 1986; 29:82.
  60. Ragab AH, Gilkerson E, Myers M. The effect of 6-mercaptopurine and allopurinol on granulopoiesis. Cancer Res 1974; 34:2246.
  61. Allopurinol and cytotoxic drugs. Interaction in relation to bone marrow depression. Boston Collaborative Drug Surveillance Program. JAMA 1974; 227:1036.
  62. Singh JA, Strand V. Gout is associated with more comorbidities, poorer health-related quality of life and higher healthcare utilisation in US veterans. Ann Rheum Dis 2008; 67:1310.
  63. Elion GB. Allopurinol and other inhibitors of urate synthesis. In: Uric acid. Handbook of Experimental Pharmacology, Kelley WN, Weiner IM (Eds), Springer-Verlag, New York 1978. p.485.
  64. Rundles RW. The development of allopurinol. Arch Intern Med 1985; 145:1492.
  65. Beardmore TD, Kelley WN. Mechanism of allopurinol-mediated inhibition of pyrimidine biosynthesis. J Lab Clin Med 1971; 78:696.
  66. Avena-Woods C, Hilas O. Febuxostat (Uloric), A New Treatment Option for Gout. Pharmacy & Therapeutics 2010; 35:82.
  67. Febuxostat (Uloric) for chronic treatment of gout. Med Lett Drugs Ther 2009; 51:37.
  68. Uloric (febuxostat): Complete prescribing information www.uloric.com (Accessed on June 08, 2009).
  69. Health Canada Summary Safety Review - ULORIC (febuxostat) - Assessing the Potential Risk of Heart Failure http://www.hc-sc.gc.ca/dhp-mps/medeff/reviews-examens/uloric2-eng.php#fnb1 (Accessed on April 10, 2016).
  70. Febuxostat and cardiac failure. WHO pharmaceuticals newsletter. No.5, 2014, pp 11-15. http://www.who.int/medicines/publications/PharmNewsletter5_14..pdf (Accessed on April 10, 2016).
  71. Becker MA, Schumacher HR Jr, Wortmann RL, et al. Febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase: a twenty-eight-day, multicenter, phase II, randomized, double-blind, placebo-controlled, dose-response clinical trial examining safety and efficacy in patients with gout. Arthritis Rheum 2005; 52:916.
  72. Seth R, Kydd AS, Buchbinder R, et al. Allopurinol for chronic gout. Cochrane Database Syst Rev 2014; :CD006077.
  73. Perez-Ruiz F, Gomez-Ullate P, Amenabar JJ, et al. Long-term efficacy of hyperuricaemia treatment in renal transplant patients. Nephrol Dial Transplant 2003; 18:603.
  74. Yu TF, Roboz J, Johnson S, Kaung C. Studies on the metabolism of D-penicillamine and its interaction with probenecid in cystinuria and rheumatoid arthritis. J Rheumatol 1984; 11:467.
  75. Fam AG. Difficult gout and new approaches for control of hyperuricemia in the allopurinol-allergic patient. Curr Rheumatol Rep 2001; 3:29.
  76. Reinders MK, van Roon EN, Jansen TL, et al. Efficacy and tolerability of urate-lowering drugs in gout: a randomised controlled trial of benzbromarone versus probenecid after failure of allopurinol. Ann Rheum Dis 2009; 68:51.
  77. Enomoto A, Kimura H, Chairoungdua A, et al. Molecular identification of a renal urate anion exchanger that regulates blood urate levels. Nature 2002; 417:447.
  78. Anzai N, Ichida K, Jutabha P, et al. Plasma urate level is directly regulated by a voltage-driven urate efflux transporter URATv1 (SLC2A9) in humans. J Biol Chem 2008; 283:26834.
  79. FDA approves Zurampic to treat high blood uric acid levels associated with gout. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm478791.htm (Accessed on December 24, 2015).
  80. Highlights of prescribing information. ZURAMPIC® (lesinurad). http://www.azpicentral.com/zurampic/zurampic.pdf (Accessed on December 24, 2015).
  81. Bardin T, Keenan RT, Khanna PP, et al. Lesinurad in combination with allopurinol: a randomised, double-blind, placebo-controlled study in patients with gout with inadequate response to standard of care (the multinational CLEAR 2 study). Ann Rheum Dis 2017; 76:811.
  82. Saag KG, Fitz-Patrick D, Kopicko J, et al. Lesinurad Combined With Allopurinol: A Randomized, Double-Blind, Placebo-Controlled Study in Gout Patients With an Inadequate Response to Standard-of-Care Allopurinol (a US-Based Study). Arthritis Rheumatol 2017; 69:203.
  83. Weinberger A, Schindel B, Liberman UA, et al. Calciuric effect of probenecid in gouty patients. Isr J Med Sci 1983; 19:377.
  84. FDA News Release. FDA approves Zurampic to treat high blood uric acid levels associated with gout http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm478791.htm (Accessed on January 31, 2016).
  85. PASCALE LR, DUBIN A, BRONSKY D, HOFFMAN WS. Inhibition of the uricosuric action of benemid by salicylate. J Lab Clin Med 1955; 45:771.
  86. Harris M, Bryant LR, Danaher P, Alloway J. Effect of low dose daily aspirin on serum urate levels and urinary excretion in patients receiving probenecid for gouty arthritis. J Rheumatol 2000; 27:2873.
  87. Würzner G, Gerster JC, Chiolero A, et al. Comparative effects of losartan and irbesartan on serum uric acid in hypertensive patients with hyperuricaemia and gout. J Hypertens 2001; 19:1855.
  88. Feher MD, Hepburn AL, Hogarth MB, et al. Fenofibrate enhances urate reduction in men treated with allopurinol for hyperuricaemia and gout. Rheumatology (Oxford) 2003; 42:321.
  89. Pegloticase (Krystexxa) IV infusion. Arthritis Advisory Committee Meeting. June 16, 2009. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ArthritisDrugsAdvisoryCommittee/UCM167777.pdf (Accessed on October 05, 2010).
  90. Sundy JS, Baraf HS, Yood RA, et al. Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment: two randomized controlled trials. JAMA 2011; 306:711.
  91. Krystexxa. US Food and Drug Administration (FDA) approved product information; East Brunswick, NJ: Savient Pharmaceuticals, Inc; April 2012.
  92. American College of Rheumatology Hotline: Pegloticase and concomitant urate-lowering therapies. http://www.rheumatology.org/publications/hotline/2012_01_18_pegloticase.asp (Accessed on January 23, 2012).
  93. Lipsky PE, Calabrese LH, Kavanaugh A, et al. Pegloticase immunogenicity: the relationship between efficacy and antibody development in patients treated for refractory chronic gout. Arthritis Res Ther 2014; 16:R60.
  94. Becker MA, Baraf HS, Yood RA, et al. Long-term safety of pegloticase in chronic gout refractory to conventional treatment. Ann Rheum Dis 2013; 72:1469.
  95. Baraf HS, Becker MA, Gutierrez-Urena SR, et al. Tophus burden reduction with pegloticase: results from phase 3 randomized trials and open-label extension in patients with chronic gout refractory to conventional therapy. Arthritis Res Ther 2013; 15:R137.
  96. Richette P, Brière C, Hoenen-Clavert V, et al. Rasburicase for tophaceous gout not treatable with allopurinol: an exploratory study. J Rheumatol 2007; 34:2093.
  97. Rozenberg S, Roche B, Dorent R, et al. Urate-oxidase for the treatment of tophaceous gout in heart transplant recipients. A report of three cases. Rev Rhum Engl Ed 1995; 62:392.
  98. Phillips M, Hunt RF, Shergy WJ, Hernandez J. Urate-oxidase in the treatment of severe tophaceous gout with hyperuricemia refractory to high-dose allopurinol: case report and review. Arthritis Rheum 2000; 43:S401.
  99. Vogt B. Urate oxidase (rasburicase) for treatment of severe tophaceous gout. Nephrol Dial Transplant 2005; 20:431.
  100. Sundy JS, Becker MA, Baraf HS, et al. Reduction of plasma urate levels following treatment with multiple doses of pegloticase (polyethylene glycol-conjugated uricase) in patients with treatment-failure gout: results of a phase II randomized study. Arthritis Rheum 2008; 58:2882.
  101. Liu-Bryan R, Scott P, Sydlaske A, et al. Innate immunity conferred by Toll-like receptors 2 and 4 and myeloid differentiation factor 88 expression is pivotal to monosodium urate monohydrate crystal-induced inflammation. Arthritis Rheum 2005; 52:2936.
  102. Martinon F, Pétrilli V, Mayor A, et al. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 2006; 440:237.
  103. So A, De Smedt T, Revaz S, Tschopp J. A pilot study of IL-1 inhibition by anakinra in acute gout. Arthritis Res Ther 2007; 9:R28.
  104. Terkeltaub R, Sundy JS, Schumacher HR, et al. The interleukin 1 inhibitor rilonacept in treatment of chronic gouty arthritis: results of a placebo-controlled, monosequence crossover, non-randomised, single-blind pilot study. Ann Rheum Dis 2009; 68:1613.
  105. Schlesinger N, Alten RE, Bardin T, et al. Canakinumab for acute gouty arthritis in patients with limited treatment options: results from two randomised, multicentre, active-controlled, double-blind trials and their initial extensions. Ann Rheum Dis 2012; 71:1839.
  106. Schumacher HR Jr, Evans RR, Saag KG, et al. Rilonacept (interleukin-1 trap) for prevention of gout flares during initiation of uric acid-lowering therapy: results from a phase III randomized, double-blind, placebo-controlled, confirmatory efficacy study. Arthritis Care Res (Hoboken) 2012; 64:1462.
  107. Sundy JS, Schumacher HR, Kivitz A, et al. Rilonacept for gout flare prevention in patients receiving uric acid-lowering therapy: results of RESURGE, a phase III, international safety study. J Rheumatol 2014; 41:1703.
  108. YU TF, GUTMAN AB. Efficacy of colchicine prophylaxis in gout. Prevention of recurrent gouty arthritis over a mean period of five years in 208 gouty subjects. Ann Intern Med 1961; 55:179.
  109. Yü T. The efficacy of colchicine prophylaxis in articular gout--a reappraisal after 20 years. Semin Arthritis Rheum 1982; 12:256.
  110. Borstad GC, Bryant LR, Abel MP, et al. Colchicine for prophylaxis of acute flares when initiating allopurinol for chronic gouty arthritis. J Rheumatol 2004; 31:2429.
  111. Paulus HE, Schlosstein LH, Godfrey RG, et al. Prophylactic colchicine therapy of intercritical gout. A placebo-controlled study of probenecid-treated patients. Arthritis Rheum 1974; 17:609.
  112. Justiniano M, Dold S, Espinoza LR. Rapid onset of muscle weakness (rhabdomyolysis) associated with the combined use of simvastatin and colchicine. J Clin Rheumatol 2007; 13:266.
  113. Simkin PA, Gardner GC. Colchicine use in cyclosporine treated transplant recipients: how little is too much? J Rheumatol 2000; 27:1334.
  114. Colchicine and other drugs for gout. Med Lett Drugs Ther 2009; 51:93.
  115. URL Pharma launches Colcrys patient assistance program www.colcrys.com/assets/pdf/Colcrys PAP Release 122309.pdf (Accessed on February 08, 2010).
  116. Ferraz MB. An evidence based appraisal of the management of nontophaceous interval gout. J Rheumatol 1995; 22:1618.
  117. Hung IF, Wu AK, Cheng VC, et al. Fatal interaction between clarithromycin and colchicine in patients with renal insufficiency: a retrospective study. Clin Infect Dis 2005; 41:291.
  118. Dalbeth N, Kumar S, Stamp L, Gow P. Dose adjustment of allopurinol according to creatinine clearance does not provide adequate control of hyperuricemia in patients with gout. J Rheumatol 2006; 33:1646.
  119. Stamp LK, O'Donnell JL, Zhang M, et al. Using allopurinol above the dose based on creatinine clearance is effective and safe in patients with chronic gout, including those with renal impairment. Arthritis Rheum 2011; 63:412.
  120. Saag KG, Whelton A, Becker MA, et al. Impact of Febuxostat on Renal Function in Gout Patients With Moderate-to-Severe Renal Impairment. Arthritis Rheumatol 2016; 68:2035.
  121. Garg JP, Chasan-Taber S, Blair A, et al. Effects of sevelamer and calcium-based phosphate binders on uric acid concentrations in patients undergoing hemodialysis: a randomized clinical trial. Arthritis Rheum 2005; 52:290.
  122. Nakamichi K, Tachibana S. Cubital tunnel syndrome caused by tophaceous gout. J Hand Surg Br 1996; 21:559.
  123. Vervaeck M, De Keyser J, Pauwels P, et al. Sudden hypotonic paraparesis caused by tophaceous gout of the lumbar spine. Clin Neurol Neurosurg 1991; 93:233.
  124. Murshid WR, Moss TH, Ettles DF, Cummins BH. Tophaceous gout of the spine causing spinal cord compression. Br J Neurosurg 1994; 8:751.
  125. Kumar S, Gow P. A survey of indications, results and complications of surgery for tophaceous gout. N Z Med J 2002; 115:U109.
  126. O'Duffy JD, Hunder GG, Kelly PJ. Decreasing prevalence of tophaceous gout. Mayo Clin Proc 1975; 50:227.
  127. Becker MA, Chohan S. We can make gout management more successful now. Curr Opin Rheumatol 2008; 20:167.
  128. Nakayama DA, Barthelemy C, Carrera G, et al. Tophaceous gout: a clinical and radiographic assessment. Arthritis Rheum 1984; 27:468.
  129. Lawry GV 2nd, Fan PT, Bluestone R. Polyarticular versus monoarticular gout: a prospective, comparative analysis of clinical features. Medicine (Baltimore) 1988; 67:335.
  130. Macfarlane DG, Dieppe PA. Diuretic-induced gout in elderly women. Br J Rheumatol 1985; 24:155.
  131. Lally EV, Zimmermann B, Ho G Jr, Kaplan SR. Urate-mediated inflammation in nodal osteoarthritis: clinical and roentgenographic correlations. Arthritis Rheum 1989; 32:86.
  132. Lin HY, Rocher LL, McQuillan MA, et al. Cyclosporine-induced hyperuricemia and gout. N Engl J Med 1989; 321:287.
  133. Burack DA, Griffith BP, Thompson ME, Kahl LE. Hyperuricemia and gout among heart transplant recipients receiving cyclosporine. Am J Med 1992; 92:141.
  134. Richette P, Doherty M, Pascual E, et al. 2016 updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis 2017; 76:29.
  135. Khanna D, Khanna PP, Fitzgerald JD, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 2: therapy and antiinflammatory prophylaxis of acute gouty arthritis. Arthritis Care Res (Hoboken) 2012; 64:1447.
  136. Yamanaka H, Japanese Society of Gout and Nucleic Acid Metabolism. Japanese guideline for the management of hyperuricemia and gout: second edition. Nucleosides Nucleotides Nucleic Acids 2011; 30:1018.
  137. Qaseem A, Harris RP, Forciea MA, Clinical Guidelines Committee of the American College of Physicians. Management of Acute and Recurrent Gout: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med 2017; 166:58.
  138. Kiltz U, Smolen J, Bardin T, et al. Treat-to-target (T2T) recommendations for gout. Ann Rheum Dis 2016; 76:632.