The Treatment of Gout

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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.

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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.

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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.

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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.

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Anti-inflammatory prophylaxis should begin at the same time that ULT is initiated, since an acute attack is likely due to a transient rise in the sUA level resulting from mobilization of MSU crystals. Colchicine, which is the only drug approved by the FDA for prophylaxis of an acute gout attack, can be used daily in a low-dose regimen (0.6 mg once or twice daily) for up to 6 months.^17,26 Alternatively, an NSAID can be used.¹⁷

One recent investigation pooled the results of 3 phase III clinical trials of ULT in 4101 patients with gout.²⁸ Patients received prophylaxis for 8 weeks or 6 months with low-dose colchicine 0.6 mg once daily or the combination of naproxen 250 mg twice daily with lansoprazole 15 mg once daily. The incidence of acute gout attacks increased sharply (up to 40%) at the end of 8 weeks of prophylaxis with either colchicine or naproxen and then declined steadily, whereas the rates of acute attacks were consistently low (3% to 5%) at the end of 6 months of prophylaxis with either colchicine or naproxen/lansoprazole. With the 8-week prophylaxis regimen, diarrhea was more common in the colchicine group (n = 993) than in the naproxen group (n = 829) (8.4% vs 2.7%, respectively; P < .001). With the 6-month prophylaxis regimen, liver function abnormalities (7.7% vs 4.3%; P = .023) and headache (2.8% vs 0.9%; P = .037) were more common with colchicine (n = 1807) than naproxen, while gastrointestinal/abdominal pains (3.2% vs 1.2%; P = .012) and dental/oral soft tissue infections (2.3% vs 0.6%; P = .006) were more common with naproxen (n = 346) than colchicine.

Uricostatic Agents

Uricostatic therapy with a xanthine oxidase inhibitor (ie, allopurinol or febuxostat) is the most commonly used ULT. Allopurinol is effective in lowering the sUA level and has been shown to lower the rates of all-cause mortality and cardiovascular events, and, in patients with chronic kidney disease, slow the progression of renal disease.^29,30 One key point that must be kept in mind is that the efficacy of allopurinol to lower the sUA level is dose-dependent, although limited safety data are available for doses >300 mg per day.^14,31,32 One recent prospective clinical trial showed that 26% of patients achieved an sUA level of 5 mg/dL or less following 2 months of treatment with allopurinol 300 mg per day compared with 78% of those who subsequently doubled the dose to 300 mg twice daily.³¹ Two patients discontinued treatment with allopurinol because of an AE. Finally, the dose of allopurinol must be adjusted based on renal function to minimize the risk of AEs, particularly skin rashes.³³

Febuxostat is also effective in lowering the sUA level. In patients with an sUA level of 8.0 mg/dL or higher and a creatinine clearance of 50 mL/min or higher at baseline, an sUA level of less than 6.0 mg/dL was achieved in 53% of patients treated with febuxostat 80 mg (n = 256) versus 21% of patients treated with allopurinol 300 mg once daily (n = 253) after 1 year (P < .001).³⁴ The most frequent treatment-related AE was liver function abnormality, which occurred in 4% of patients in each group. Results of a 6-month trial showed that achievement of an sUA level of less than 6.0 mg/dL was achieved in 45% and 67% of patients treated with febuxostat 40 mg or 80 mg daily, respectively, and 42% of those treated with allopurinol 300 mg (200 mg in moderate renal impairment) daily.³⁵ Febuxostat also has been shown to slow the progression of, or even stabilize, renal function.³⁶

Treatment plan (continued):

For an acute gout attack: Continue colchicine as needed
ULT: Initiate allopurinol 100 mg once daily; increase to 200 mg once daily in 1 week, and 300 mg once daily in another week
- -Alternatively, initiate febuxostat 40 mg once daily; increase to 80 mg once daily if an sUA level of less than 6.0 mg/dL is not achieved within 2 weeks
For prophylaxis of an acute attack when initiating ULT: Initiate colchicine 0.6 mg once daily; may increase to 0.6 mg twice daily if needed
- -Alternatively, initiate naproxen 250 mg twice daily with a proton pump inhibitor
Measure sUA in 1 month; if the sUA level is greater than 6.0 mg/dL, increase allopurinol to 200 mg twice daily
- -Measure sUA in 1 month; if the sUA level is still greater than 6.0 mg/dL, increase allopurinol to 300 mg twice daily
Implement the care plan ( TABLE )²⁷
- -Inquire about and address issues to promote adherence and self-management
- -Discuss the most common AEs with allopurinol and colchicine and the actions the patient should take if an AE occurs
Once the sUA level is 6.0 mg/dL or less, monitor sUA annually (including serum creatinine)¹⁴