The Treatment of Gout

,

Medical Education Library

The Treatment of Gout

June 2012 · Vol. 61, No. 06 Suppl: S11-S15

References

1. Zhu Y, Pandya BJ, Choi HK. Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007-2008. Arthritis Rheum. 2011;63(10):3136-3141.

2. Weaver AL. Epidemiology of gout. Cleve Clin J Med. 2008;75(suppl 5):S9-S12.

3. Choi HK, Atkinson K, Karlson EW, Curhan G. Obesity, weight change, hypertension, diuretic use, and risk of gout in men: the health professionals follow-up study. Arch Intern Med. 2005;165(7):742-748.

4. Choi HK, Curhan G. Soft drinks, fructose consumption, and the risk of gout in men: prospective cohort study. BMJ. 2008;336(7639):309-312.

5. Choi HK, Atkinson K, Karlson EW, Willett W, Curhan G. Purine-rich foods, dairy and protein intake, and the risk of gout in men. N Engl J Med. 2004;350(11):1093-1103.

6. Choi HK, Atkinson K, Karlson EW, Willett W, Curhan G. Alcohol intake and risk of incident gout in men: a prospective study. Lancet. 2004;363(9417):1277-1281.

7. Choi HK, Ford ES, Li C, Curhan G. Prevalence of the metabolic syndrome in patients with gout: the Third National Health and Nutrition Examination Survey. Arthritis Rheum. 2007;57(1):109-115.

8. Perlstein TS, Gumieniak O, Williams GH, et al. Uric acid and the development of hypertension: the normative aging study. Hypertension. 2006;48(6):1031-1036.

9. Bos MJ, Koudstaal PJ, Hofman A, Witteman JC, Breteler MM. Uric acid is a risk factor for myocardial infarction and stroke: the Rotterdam study. Stroke. 2006;37(6):1503-1507.

10. Iseki K, Ikemiya Y, Inoue T, Iseki C, Kinjo K, Takishita S. Significance of hyperuricemia as a risk factor for developing ESRD in a screened cohort. Am J Kidney Dis. 2004;44(4):642-650.

11. Tomita M, Mizuno S, Yamanaka H, et al. Does hyperuricemia affect mortality? A prospective cohort study of Japanese male workers. J Epidemiol. 2000;10(6):403-409.

12. Campion EW, Glynn RJ, DeLabry LO. Asymptomatic hyperuricemia. Risks and consequences in the Normative Aging Study. Am J Med. 1987;82(3):421-426.

13. Mandell BF. Clinical manifestations of hyperuricemia and gout. Cleve Clin J Med. 2008;75(Suppl 5):S5-S8.

14. Hamburger M, Baraf HS, Adamson TC III, et al. 2011 Recommendations for the diagnosis and management of gout and hyperuricemia. Postgrad Med. 2011;123 (6 suppl 1):3-36.

15. 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):1312-1324.

16. Schumacher HR Jr, Boice JA, Daikh DI, et al. Randomised double blind trial of etoricoxib and indometacin in treatment of acute gouty arthritis. BMJ. 2002;324(7352):1488-1492.

17. 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 (Oxford). 2007;46(8):1372-1374.

18. Trelle S, Reichenbach S, Wandel S, et al. Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. BMJ. 2011;342:c7086.-

19. Schmidt M, Christiansen CF, Mehnert F, Rothman KJ, Sorensen HT. Non-steroidal anti-inflammatory drug use and risk of atrial fibrillation or flutter: population based case-control study. BMJ. 2011;343:d3450.-

20. NSAIDS and chronic kidney disease. US Centers for Disease Control and Prevention. http://www.cdc.gov/diabetes/news/docs/nsaid_video.htm. Published 2012. Accessed April 22, 2012.

21. Gislason GH, Rasmussen JN, Abildstrom SZ, et al. Increased mortality and cardiovascular morbidity associated with use of nonsteroidal anti-inflammatory drugs in chronic heart failure. Arch Intern Med. 2009;169(2):141-149.

22. Janssens HJ, Lucassen PL, Van de Laar FA, Janssen M, Van de Lisdonk EH. Systemic corticosteroids for acute gout. Cochrane Database Syst Rev. 2008;(2):CD005521.-

23. Janssens HJ, Janssen M, van de Lisdonk EH, van Riel PL, van Weel C. Use of oral prednisolone or naproxen for the treatment of gout arthritis: a double-blind, randomised equivalence trial. Lancet. 2008;371(9627):1854-1860.

24. Schlesinger N, Schumacher R, Catton M, Maxwell L. Colchicine for acute gout. Cochrane Database Syst Rev. 2006;(4):CD006190.-

25. Terkeltaub RA, Furst DE, Bennett K, Kook KA, Crockett RS, Davis MW. High versus low dosing of oral colchicine for early acute gout flare: Twenty-four-hour outcome of the first multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison colchicine study. Arthritis Rheum. 2010;62(4):1060-1068.

26. Colcrys [package insert]. Philadelphia, PA: AR Scientific, Inc.; 2011.

27. Becker MA, Ruoff GE. What do I need to know about gout? J Fam Pract. 2010;59(6 suppl):S1-S8.

28. Wortmann RL, Macdonald PA, Hunt B, Jackson RL. Effect of prophylaxis on gout flares after the initiation of urate-lowering therapy: analysis of data from three phase III trials. Clin Ther. 2010;32(14):2386-2397.

29. Luk AJ, Levin GP, Moore EE, Zhou XH, Kestenbaum BR, Choi HK. Allopurinol and mortality in hyperuricaemic patients. Rheumatology (Oxford). 2009;48(7):804-806.

30. 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(8):1388-1393.

31. Reinders MK, Haagsma C, Jansen TL, et al. A randomised controlled trial on the efficacy and tolerability with dose escalation of allopurinol 300-600 mg/day versus benzbromarone 100-200 mg/day in patients with gout. Ann Rheum Dis. 2009;68(6):892-897.

32. 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(2):412-421.

33. Zyloprim [package insert]. San Diego, CA: Prometheus Laboratories Inc.; 2003.

34. 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(23):2450-2461.

35. 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:doi:10.1186/ar2978.

36. Whelton A, Macdonald PA, Zhao L, Hunt B, Gunawardhana L. Renal function in gout: long-term treatment effects of febuxostat. J Clin Rheumatol. 2011;17(1):7-13.

Untreated or poorly treated gout usually leads to further acute attacks and progressive joint and tissue damage. In addition, gout and hyperuricemia serve as risk factors for other diseases. Adults with gout are 3 times as likely to develop metabolic syndrome as adults without gout.⁷ An elevated sUA level is also an independent risk factor for the development of hypertension (RR, 1.1), as well as myocardial infarction (MI; RR, 1.9), and stroke (RR, 1.6).^8,9 An increasing sUA level also increases the risk of renal failure.^10,11 In a study of 49,413 men followed for a mean of 5.4 years, the age-adjusted RR of renal failure was 1.5 in men with an sUA level of 6.5 to 8.4 mg/dL and 8.5 in men with an sUA level of 8.5 to 13.0 mg/dL compared with men with an sUA level of 5.0 to 6.4 mg/dL.¹¹

Clinical Presentation

The deposition of monosodium urate (MSU) crystals in joints and tissues is very common and typically causes no signs or symptoms in the majority of persons. Even in men with an sUA level of 9 mg/dL or greater, the cumulative incidence of gouty arthritis has been found to be 22% over 5 years.¹² However, as crystal deposition progresses, acute, painful attacks occur more frequently, with the development of chronic tophaceous gout after several years.¹³

Laboratory results for DB:

Serum uric acid, 7.9 mg/dL
White blood cell count, 15,800/mm³
Serum creatinine, 1.2 mg/dL (estimated creatinine clearance, 90 mL/min)
Erythrocyte sedimentation rate, 23 mm/h
Low-density lipoprotein cholesterol (nonfasting), 127 mg/dL

Laboratory confirmation of hyperuricemia together with the pain, swelling, and tenderness of DB’s toe and ankle, other findings from his medical history and physical exam (eg, the use of aspirin daily), and exclusion of alternative diagnoses, such as septic arthritis, enable the family physician to arrive at a presumptive diagnosis of gouty arthritis. Aspiration of MSU crystals from DB’s toe or ankle is the gold standard and would allow for a definitive diagnosis. Although the sUA level was found to be high, it should be noted that a normal sUA level is often found during an acute attack; should this occur, the sUA level should be checked again 1 to 2 weeks after the acute attack has resolved.

Goals of Treatment

The cornerstone of gout management is daily, long-term treatment with urate-lowering therapy (ULT) combined with as-needed treatment for an acute attack. In addition, since initiation of ULT mobilizes MSU crystals, which often leads to a short-term increase in acute attacks, prophylaxis with an appropriate anti-inflammatory therapy is recommended at the time ULT is initiated.¹⁴

The therapeutic goals of gout treatment are 2-pronged: treatment of an acute gout attack and management of chronic gout. For an acute attack, the goals are to exclude a diagnosis of septic arthritis; reduce inflammation and terminate the attack; and seek, assess, and control associated diseases, such as diabetes mellitus, hypertension, hyperlipidemia, and CVD. If this latter goal is not possible during the acute attack, plans should be made to assess associated diseases once the acute attack has resolved.¹⁴ Lowering the sUA level is not a goal of therapy for an acute attack, but it is the primary goal of ULT for chronic gout. Lowering the sUA level to less than 6.0 mg/dL, which is well below the saturation point of urate in most biological fluids, is intended to prevent further acute attacks, tophus formation, and tissue damage.¹⁴

Treatment of an Acute Attack

The mainstay of treatment for an acute attack is anti-inflammatory therapy to reduce pain and inflammation.¹⁴ Therapy should be initiated at the onset of the attack and continued until the attack is terminated, which is typically 1 to 2 weeks. Anti-inflammatory therapy traditionally has in-cluded colchicine, a nonsteroidal anti-inflammatory drug (NSAID), or a corticosteroid.¹⁴

Nonsteroidal Anti-inflammatory Drugs

The NSAIDs are all thought to provide similar efficacy when used in maximum doses.^15,16 Since gastrointestinal toxicity is a concern with NSAIDs, coadministration of a proton pump inhibitor, H₂ antagonist, or misoprostol is advised for patients with an increased risk of peptic ulcers, bleeds, or perforations.¹⁷ The risk of MI, stroke, cardiovascular death, and atrial fibrillation/flutter with NSAID therapy should be considered, especially because gout often coexists with cardiovascular disorders.^15,18,19 Furthermore, NSAIDs are contraindicated in patients with heart failure or renal insufficiency.^20,21

Corticosteroids. A systematic review of clinical trials involving systemic corticosteroids that found a few prospective trials of low to moderate quality concluded that there was inconclusive evidence for the efficacy and effectiveness of corticosteroids in the treatment of acute gout.²² No serious adverse events (AEs) were reported. A more recent prospective trial found comparable pain reduction and incidence of AEs with naproxen 500 mg twice daily and prednisolone 35 mg once daily for 5 days in patients with monoarticular gout.²³ Furthermore, clinical experience indicates that intra-articular aspiration and injection of a long-acting corticosteroid is an effective and safe treatment for an acute attack.^14,15 Corticosteroids may be useful in patients who have an inadequate response to, are intolerant of, or have a contraindication to NSAIDs and colchicine.^14,15