Abstract
Gout is common in the elderly and its management is frequently complicated by the presence of co-morbid conditions and medications prescribed for other conditions. The management of gout is 2-fold: (i) treatment of the acute attack to rapidly resolve the pain and inflammation; and (ii) long-term urate-lowering therapy (ULT) to prevent further gouty episodes. NSAIDs, colchicine, corticosteroids and more recently interleukin (IL)-1 inhibitors are effective treatments for acute gout. The choice of agent is determined by the patient’s age, co-morbidities and concomitant medications. Renal impairment is of particular concern in the elderly and may preclude the use of NSAIDs and colchicine. The IL-1 inhibitors are rapidly effective but data in the elderly are limited. ULT aiming for a serum urate <0.36mmol/L, or lower in severe tophaceous gout, is critical for the long-term management of gout. Urate lowering can be achieved by inhibiting the production of uric acid through xanthine oxidase inhibition (allopurinol, febuxostat), increasing uric acid excretion via the kidneys (uricosuric agents: probenecid, benzbromarone) or dissolving uric acid to the more water soluble allantoin (recombinant uricases: pegloticase, rasburicase). Allopurinol is the most commonly used ULT, but there is no consensus on dosing in renal impairment. Febuxostat is effective at lowering serum urate, but there are limited data in the elderly and patients with renal impairment. Furthermore, there are concerns about cardiovascular safety. Probenecid is ineffective in patients with renal impairment (creatinine clearance <60 mL/min) and the availability of benzbromarone is limited because of concerns about its hepatotoxicity. The recombinant uricases provide an exciting new therapeutic option, but there are limited data for their use in the elderly. These agents may be particularly useful in patients with a high urate burden (e.g. those with tophi); however, they may precipitate a severe flare of gout and this will require treatment in its own right. Careful consideration of the patient’s concomitant medications is required as many drugs increase serum urate. Successful urate lowering will ultimately reduce gout flares and thereby improve patient quality of life.
Similar content being viewed by others
References
De Leonardis F, Govoni M, Colina M, et al. Elderly-onset gout: a review. Rheumatol Int 2007; 28: 1–6
Munan L, Kelly A, Petitclerc C. Population serum urate levels and their correlates: the Sherbrooke Regional Study. Am J Epidemiol 1976 Apr; 103(4): 369–82
Acheson RM, Chan Y-K. New Haven survey of joint diseases: the prediction of serum uric acid in a general population. J Chronic Dis 1969 Jan; 21(8): 543–53
Alatalo PI, Koivisto HM, Hietala JP, et al. Gender-dependent impacts of body mass index and moderate alcohol consumption on serum uric acid: an index of oxidant stress status? Free Radic Biol Med 2009 Apr 15; 46(8): 1233–8
Hak AE, Choi HK. Menopause, postmenopausal hormone use and serum uric acid levels in US women: the Third National Health and Nutrition Examination Survey. Arthritis Res Ther 2008; 10(5): R116
Sumino H, Ichikawa S, Kanda T, et al. Reduction of serum uric acid by hormone replacement therapy in postmeno-pausal women with hyperuricaemia. Lancet 1999 Aug 21; 354(9179): 650
Perez-Ruiz F, Calabozo M, Erauskin G, et al. Renal un-derexcretion of uric acid is present in patients with apparent high urinary uric acid output. Arthritis Care Res 2002; 47(6): 610–3
Coresh J, Astor B, Greene T, et al. Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey. Am J Kidney Dis 2003; 41(1): 1–12
Wyatt C, Kim M, Winston J. Therapy insight: how changes in renal function with increasing age affect cardiovascular drug prescribing. Nat Clin Pract Cardiovasc Med 2006; 3(2): 102–9
Reinders M, Van Roon E, Jansen T, 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: 51–6
Smythe C, Percy J. Comparison of indomethacin and phenylbutazone in acute gout. Ann Rheum Dis 1973; 32: 351–3
Altman R, Honig S, Levin J, et al. Ketoprofen versus in-domethacin in patients with acute gouty arthritis: a multicenter, double blind comparative study. J Rheumatol 1988; 15(9): 1422–6
Ruotsi A, Vainio U. Treatment of acute gouty arthritis with proquazone and indomethacin. Scand J Rheumatol Suppl 1978; (21): 15–7
Weiner G, White S, Weitzner R, et al. Double-blind study of fenoprofen versus phenylbutazone in acute gouty arthritis. Arthritis Rheum 1979; 22: 425–6
Shrestha M, Morgan D, Moredon J, et al. Randomized double-blind comparison of the analgesic efficacy of intramuscular ketorolac and oral indomethacin in the treatment of acute gouty arthritis. Ann Emerg Med 1995; 26(6): 682–6
Maccagno A, Di Giorgio E, Romanowicz A. Effectiveness of etodolac (‘Lodine’) compared with naproxen in patients with acute gout. Curr Med Res Opin 1991; 12(7): 423–9
Fraser R, Davis R, Walker F. Comparative trial of aza-propazone and indomethacin plus allopurinol in acute gout and hyperuricaemia. J Royal Coll Gen Pract 1987; 37: 409–11
Burmester G, Lanas A, Biasucci L, et al. The appropriate use of non-steroidal anti-inflammatory drugs in rheumatic disease: opinions of a multidisciplinary European expert panel. Ann Rheum Dis 2011; 70(5): 818–22
Boers M, Tangelder M, van Ingen H, et al. The rate of NSAID-induced endoscopic ulcers increases linearly but not exponentially with age: a pooled analysis of 12 randomised trials. Ann Rheum Dis 2007; 66: 417–8
Franceschi M, Di Mario F, Leandro G, et al. Acid-related disorders in the elderly. Best Pract Res Clin Gastroenterol 2009; 23(6): 839–48
Johnson A, Nguyen T, Day R. Do nonsteroidal anti-inflammatory drugs affect blood pressure? Ann Intern Med 1994; 121(4): 289–300
Rubin B, Burton R, Navarra S, et al. Efficacy and safety profile of treatment with etoricoxib 120 mg once daily compared with indomethacin 50 mg three times daily in acute gout. Arthritis Rheum 2004; 50(2): 598–606
Schumacher HR, Boicee J, Daikh D, et al. Randomised double blind trial of etoricoxib and indomethacin in treatment of acute gouty arthritis. BMJ 2002; 324: 1488–92
Willburger R, Mysler E, Derbot J, et al. Lumiracoxib 400 mg once daily is comparable to indomethacin 50 mg three times daily for the treatment of acute flares of gout. Rheumatology 2007; 46(7): 1126–32
Schumacher H, Berger M, Li-Yu J, et al. Efficacy and tol-erability of celecoxib in the treatment of moderate to extreme pain associated with acute gouty arthritis: a randomized controlled trial [abstract]. Arthritis Rheum 2010; 62(10 Suppl.): S63
Rodriguez L, Gonzalez-Perez A, Bueno H, et al. NSAID use selectively increases the risk of non-fatal myocardial infarction: a systematic review of randomised trials and observational studies. PLOS One 2011; 6: e16780
Barkin R, Beckerman M, Blum S, et al. Should nonsteroidal anti-inflammatory drugs (NSAIDs) be prescribed to the older adult? Drugs Aging 2010; 27: 775–89
Janssens H, Janssen M, van de Lisdonk E, et al. Use of oral prednisolone or naproxen for the treatment of gout arthritis: a double-blind, randomised equivalence trial. Lancet 2008; 371: 1854–60
Man C, Cheung I, Cameron P, et al. Comparison of oral prednisolone/paracetamol and oral indomethacin/paracetamol combination therapy in the treatment of acute gout like arthritis: a double-blind, randomized, controlled trial. Ann Emerg Med 2007; 49(5): 670–7
Ritter J, Kerr L, Valeriano-Marcet J, et al. ACTH revisited: effective treatment for acute crystal induced synovitis in patients with multiple medical problems. J Rheumatol 1994; 21: 696–9
Taylor C, Brooks N, Kelley K. Corticotropin for acute management of gout. Ann Pharmacother 2001; 35(3): 365–8
Axelrod D, Preston S. Comparison of parenteral adreno-corticotropic hormone with oral indomethacin in the treatment of acute gout. Arthritis Rheum 1988; 31(6): 803–5
Siegel L, Alloway J, Nashel D. Comparison of adreno-corticotropic hormone and triamcinolone acetonide in the treatment of acute gouty arthritis. J Rheumatol 1994; 21(7): 1325–7
Ahern M, McCredie M, Reid C, et al. Does colchicine work? The results of the first controlled study in acute gout. Aust NZ J Med 1987; 17: 301–4
Terkeltaub R, Furst D, Bennett K, et al. High versus low dosing of oral colchicine for early acute gout flare. Arthritis Rheum 2010; 62(4): 1060–8
Terkeltaub R. Colchicine update: 2008. Semin Arthritis Rheum 2009; 38: 411–9
Kuncl R, Duncan G, Watson D, et al. Colchicine myopathy and neuropathy. N Engl J Med 1987; 316(25): 1562–8
Wallace S, Singer J, Duncan G, et al. Renal function predicts colchicine toxicity: guidelines for the prophylactic use of colchicine in gout. J Rheumatol 1991; 18(2): 264–9
Mikuls T, MacLean C, Oliveri J, et al. Quality of care indicators for gout management. Arthritis Rheum 2004; 50(3): 937–43
Pope R, Tschopp J. The role of interleukin-1 and the in-flammasome in gout: implications for therapy. Arthritis Rheum 2007; 56(10): 3183–8
So A, De Smedt T, Revas S, et al. A pilot study of IL-1 inhibition by anakinra in acute gout. Arthritis Res Ther 2007; 9: R28
Terkeltaub R, Sundy J, Schumacher HR, et al. The inter-leukin1 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: 1613–7
So A, De Meulemeester M, Pikhlak A, et al. Canakinumab for the treatment of acute flares in difficult-to-treat gouty arthritis: results of a multicenter, phase II, dose ranging study. Arthritis Rheum 2010; 62(10): 3064–76
Perez-Ruiz F, Liote F. Lowering serum uric acid levels: what is the optimal target for improving clinical outcomes in gout? Arthritis Rheum 2007; 57: 1324–8
Stamp LK, Chapman PT. Existing and emerging therapies for acute gout and long-term urate lowering. Curr Rheu-matol Rev 2011;7: 141–51
Hande K, Noone R, Stone W. Severe allopurinol toxicity: description and guidelines for prevention in patients with renal insufficiency. Am J Med 1984; 76: 47–56
US National Library of Medicine. Daily Medicine FDA information: allopurinol tablet [online]. Available from URL: http://dailymed.nlm.nih.gov/dailymed/search.cfm?startswith=allopurinol [Accessed 2011 Oct 1]
Jordan KM, Cameron JS, Snaith M, et al. British Society for Rheumatology and British Health Professionals in Rheumatology guideline for the management of gout. Rheumatology 2007; 46(8): 1372–4
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(10): 1312–4
Bellomo G, Venanzi S, Verdura C, et al. Association of uric acid with change in kidney function in healthy normo-tensive individuals. Am J Kid Dis 2010; 56: 264–73
Ohno I, Hsoya T, Gomi H, et al. Serum uric acid and renal prognosis in patients with IgA nephropathy. Nephron 2001; 87(4): 333–9
Ficociello L, Rosolowsky E, Niswczas M, et al. Highnormal serum uric acid increases risk of early progressive renal function loss in type 1 diabetes. Diabetes Care 2010; 33(6): 1337–43
Wluka A, Ryan P, Miller A, et al. Post-cardiac transplantation gout: incidence and therapeutic complications. J Heart Lung Transplant 2000; 19: 951–6
Stamp L, O’Donnell J, Zhang M, et al. Using allopurinol above the dose based on creatinine clearance is effective and safe in chronic gout, including in those with renal impairment. Arthritis Rheum 2011; 63(2): 412–21
Venkat Raman G, Sharman V, Lee H. Azathioprine and allopurinol: a potentially dangerous combination. J Intern Med 1990; 228: 69–71
Cummins D, Sekar M, Halil O, et al. Myelosuppression associated with azathioprine-allopurinol interaction after heart and lung transplantation. Transplantation 1996; 61(11): 1661–2
Stamp L, Barclay M, O’Donnell J, et al. Relationship between serum urate and plasma oxypurinol: is there a target plasma oxypurinol concentration to achieve serum urate <0.36mmol/L? Clin Pharm Ther. In press
Iseki K, Ikemiya Y, Inoue T, et al. Significant hyperur-icaemia as a risk factor for developing ESRD in a screened cohort. Am J Kidney Dis 2004; 44(4): 642–50
Siu Y-P, Leung K-T, Tong M, et al. Use of allopurinol in slowing the progression of renal disease through its ability to lower serum uric acid level. Am J Kidney Dis 2006; 47(1): 51–9
Goicoechea M, de Vinuesa S, Verdalles U, et al. Effect of al-lopurinol in chronic kidney disease progression and cardiovascular risk. Clin J Am Soc Nephrol 2010; 5(8): 1388–93
Edwards N. The role of hyperuricaemia in vascular disorders. Curr Opin Rheum 2009; 21: 132–7
Jankowska E, Ponikowska B, Majda J, et al. Hyperur-icaemia predicts poor outcome in patients with mild to moderate chronic heart failure. Int J Cardiol 2007; 115(2): 151–5
Anker S, Doehner W, Rauchhaus M, et al. Uric acid and survival in chronic heart failure: validation and application in metabolic, functional and hemodynamic staging. Circulation 2003; 107(15): 1991–7
Luk AJ, Levin GP, Moore EE, et al. Allopurinol and mortality in hyperuricaemic patients. Rheumatology 2009 Jul; 48(7): 804–6
Thansaaoulis G, Brophy J, Richard H, et al. Gout, allo-purinol use and heart failure outcomes. Arch Intern Med 2010; 170(15): 1358–64
Kanbay M, Ozkara A, Selcoki Y, et al. Effect of treatment of hyperuricemia with allopurinol on blood pressure, creatinine clearance, and proteinuria in patients with normal renal function. Int Urol Nephrol 2007; 39(4): 1227–33
Norman A, Ang D, Ogston S, et al. Effect of high dose allopurinol on exercise in patients withy chronic stable angina: a randomised, placebo controlled crossover trial. Lancet 2010; 375: 2161–7
Rentoukas E, Tasarouhas K, Tsitsimpikou C, et al. The prognostic impact of allopurinol in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention. Int J Cardiol 2010; 145(2): 257–8
Becker M, Schumacher HR, MacDonald P, et al. Clinical efficacy and safety of successful longterm urate lowering with febuxostat or allopurinol in subjects with gout. J Rheumatol 2009; 36: 1273–82
Becker M, Schumacher HR, Espinoza L, et al. The urate-lowering efficacy and safety of febuxostat in the treatment of the hyperuricaemia of gout: the CONFIRMS trial. Arthritis Res Ther 2010; 12: R63
Schumacher HR, Becker M, Lloyd E, et al. Febuxostat in the treatment of gout: 5-yr findings of the FOCUS efficacy and safety study. Rheumatology 2009; 48: 188–94
Schumacher HR, Becker M, Wortmann R, et al. Effects of febuxostat versus allopurinol and placebo in reducing serum urate in subjects with hyperuricaemia and gout: a 28-week, phase III, randomized, double-blind, parallel-group trial. Arthritis Care Res 2008; 59(11): 1540–8
Khosravan R, Kukulka M, Wu J, et al. The effect of age and gender on pharmacokinetics, pharmacodynamics, and safety of febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase. J Clin Pharmacol 2008; 48(9): 1014–24
Krishnan E, MacDonald P, Hunt B, et al. Febuxostat versus allopurinol in the treatment of gout in subjects >65years of age: a subgroup analysis of the CONFIRMS trial [abstract]. Arthritis Rheum 2010; 62(10 Suppl.): S65
Hair P, McCormack P, Keating G. Febuxostat. Drugs 2008; 13: 1865–74
Khosravan R, Wu J, Joseph-Ridge N, et al. Pharmaco-kinetic interactions of concomitant administration of febuxostat and NSAIDs. J Clin Pharmacol 2006; 46(8): 855–66
Grabowski B, Khosravan R, Wu J, et al. Effect of hydro-chlorothiazide on the pharmacokinetics and pharmaco-dynamics of febuxostat, a non-purine selective inhibitor of xanthine oxidase. Br J Clin Pharmacol 2010; 70(1): 57–64
Khosravan R, Grabowski B, Wu J, et al. Effect of food or antacid on pharmacokinetics and pharmacodynamics of febuxostat in healthy subjects. Br J Clin Pharmacol 2008; 65(3): 355–63
Mukoyoshi M, Nishimura S, Hoshide S, et al. In vitro drug-drug interaction studies with febuxostat, a novel non-purine selective inhibitor of xanthine oxidase: plasma protein binding, identification of metabolic enzymes and cytochrome P450 inhibition. Xenobiotica 2008; 38(5): 496–510
Chohan S, Becker M. Safety and efficacy of febuxostat treatment in subjects with gout and severe allopurinol adverse reactions [abstract]. Arthritis Rheum 2010; 62(10 Suppl.): S67
Keenan R, O’Brien W, Lee K, et al. Prevalence of contraindications and prescription of pharmacologic therapies for gout. Am J Med 2011; 124: 155–63
Emmerson B. The management of gout. In: Klippel JH, Dieppe PA, editors. Rheumatology. 2nd ed. London: Mosby, 1998
Perez-Ruiz F, Gomez-Ullate P, Amenabar J, et al. Long-term efficacy of hyperuricaemia treatment in renal transplant recipients. Nephrol Dial Transplant 2003; 18: 603–6
Zurcher R, Bock H, Thiel G. Excellent uricosuric efficacy of benzbromarone in cyclosporin-A treated renal transplant patients: a prospective study. Nephrol Dial Transplant 1994; 9: 548–51
Wagayama H, Shiraki K, Sugimoto K, et al. Fulminant hepatic failure associated with benzbromarone [letter]. J Hepatol 2000; 32(5): 874
Arai M, Yokosuka O, Fujiwara K, et al. Fulminant hepatic failure associated with benzbromarone treatment: a case report. J Gastroenterol Hepatol 2002; 17(5): 625–6
Van Der Klauw M, Houtmann M, Stricker B, et al. Hepatic injury caused by benzbromarone. J Hepatol 1994; 20(3): 376–9
Lee M-H, Graham G, Williams K, et al. A benefit-risk assessment of benzbromarone in the treatment of gout: was its withdrawal from the market in the best interests of patients? Drug Saf 2008; 31(8): 643–65
Burns C, Wortmann R. Gout therapeutics: new drugs for an old disease. Lancet 2011; 377: 165–77
Pui C-H. Urate oxidase in the prophylaxis or treatment of hyperuricaemia. Semin Hematol 2001; 38 (4 Suppl. 10): 13–21
Pui C-H, Relling M, Lascombes F, et al. Urate oxidase in prevention and treatment of hyperuricaemia associated with lymphoid malignancies. Leukemia 1997; 11(11): 1813–6
Sundy J, Baraf H, Becker M, et al. Efficacy and safety of intravenous pegloticase (PGL) in subjects with treatment failure gout: results from GOUT1 and GOUT2. Arthritis Rheum 2008; 58 (9 Suppl.): S400–S1
Becker M, Treadwell E, Baraf H, et al. Immunoreactivity and clinical response to pegloticase (PGL): pooled data from GOUT1 and GOUT2, PGL phase 3 randomised, double blind, placebo controlled trials [abstract]. Arthritis Rheum 2008; 58 (9 Suppl.): S880
Terkeltaub R. Learning how and when to employ uricase as bridge therapy in refractory gout. J Rheumatol 2007; 34(10): 1955–8
Burnier M, Rutschmann B, Nussberger J, et al. Salt-dependent renal effects of an angiotensin II antagonist in healthy subjects. Hypertension 1993; 22: 339–47
Soffer B, Wright J, Pratt J, et al. Effects of losartan on a background of hydrochlorothiazide in patients with hypertension. Hypertension 1995; 26(1): 112–7
Chanard J, Toupance O, Lavaud S, et al. Amlodipine reduces cyclosporin-induced hyperuricaemia in hypertensive renal transplant recipients. Nephrol Dial Transplant 2003; 18: 2147–53
Sennesael J, Lamote J, Violet I, et al. Divergent effects of calcium channel and angiotensin converting enzyme blockade on glomerulotubular function in cyclosporin-treated renal allograft recipients. Am J Kidney Dis 1996; 27(5): 701–8
Tiitinen S, Nissilas M, Ruutsalo H, et al. Effect of non- steroidal anti-inflammatory drugs on the renal excretion of uric acid. Clin Rheumatol 1983; 2(3): 223–36
Garcia Puig J, Mateos M, Herrero E, et al. Hydrochloro-thiazide vs. spironolactone: long term metabolic complications in patients with essential hypertension. J Clin Pharmacol 1991; 31(5): 455–61
Milionis H, Kakafika A, Tsouli S, et al. Effects of statin treatment on uric acid homeostasis in patients with primary hyperlipidaemia. Am Heart J 2004; 148: 635–40
Desager J, Hulhoven R, Harvengt C. Uricosuric effect of feno-fibrate in healthy volunteers. J Clin Pharmacol 1980; 20: 560–4
Feher M, Hepburn A, Hogarth M, et al. Fenofibrate enhances urate reduction in men treated with allopurinol for hyperur-icaemia and gout. Rheumatology 2003; 42(2): 321–5
Takahashi S, Moriwaki Y, Yamamoto T, et al. Effects of combination treatment using anti-hyperuricaemic agents with fenofibrate and/or losartan on uric acid metabolism. Ann Rheum Dis 2003; 62: 572–5
Acknowledgements
No sources of funding were used to assist in the preparation of this article. The authors have no conflicts of interest that are directly relevant to the content of this article.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Stamp, L.K., Jordan, S. The Challenges of Gout Management in the Elderly. Drugs Aging 28, 591–603 (2011). https://doi.org/10.2165/11592750-000000000-00000
Published:
Issue Date:
DOI: https://doi.org/10.2165/11592750-000000000-00000