ADVERTISEMENT

The practical management of gout

July 1, 2008|Cleveland Clinic Journal of Medicine
H. Ralph Schumacher, Jr, MD;Lan X. Chen, MD, PhD
Author and Disclosure Information

H. Ralph Schumacher, Jr, MD 
Professor of Medicine, University of Pennsylvania, Philadelphia, PA 

Lan X. Chen, MD, PhD
Clinical Assistant Professor of Medicine, University of Pennsylvania, Philadelphia, PA 

Correspondence: H. Ralph Schumacher, Jr, MD, VA Medical Center, 151K, University and Woodland Avenues, Philadelphia, PA 19104; schumacr@mail.med.upenn.edu

Dr. Schumacher reported that he has received research grant support and consulting/advisory fees from TAP Pharmaceutical Products and Savient Pharmaceuticals as well as consulting/advisory fees from Pfizer, Regeneron, and Xoma.

Dr. Chen reported that he has received research grant support from TAP Pharmaceutical Products.

Dr. Schumacher received honoraria for participating in the symposium that formed the basis of this supplement and for writing this article. The honoraria were paid by Fallon Medica LLC, a medical communication company, on behalf of TAP Pharmaceutical Products, the underwriter of this supplement. TAP had no input on the content of presentations at the symposium or on this article.

This article is based on Dr. Schumacher’s lecture on this subject at the symposium that formed the basis of this supplement. Dr. Schumacher reported that he prepared his lecture, Fallon Medica transcribed his lecture, and he and Dr. Chen developed the transcript into this article without assistance from undeclared contributors. The article underwent formatting and nonsubstantive copyediting by Fallon prior to submission to the Journal.

ABSTRACT

Gout management requires a comprehensive strategy that considers both acute and chronic aspects of the disease. Acute gout flares should be treated with anti-inflammatory agents as rapidly as possible. The underlying hyperuricemia may be treated with urate-lowering agents initiated at a time appropriate for the individual patient. Successful urate lowering ultimately prevents flares and disease progression and should be started immediately in patients with advanced or tophaceous disease. When urate-lowering therapy is initiated, anti-inflammatory prophylaxis should be used to reduce the risk of flares induced by abrupt changes in urate levels. Regular monitoring of serum urate can ensure therapeutic dosing of urate-lowering agents to achieve levels below 6 mg/dL, which are associated with a reduction in flares and tophi.

KEY POINTS

  • A patient’s comorbidities and other medications should guide the choice of anti-inflammatory agent for acute attacks.
  • NSAIDs are the treatment of choice for acute gout attacks; colchicine and corticosteroids are alternatives when NSAIDs are contraindicated.
  • Urate-lowering therapy to address underyling hyperuricemia is generally a lifelong commitment, as intermittent therapy can lead to recurrent gout flares.

Allopurinol

The xanthine oxidase inhibitor allopurinol works by blocking production of uric acid and can be used in any patient with gout (Table 2). When initiating allopurinol, the safest option is to start all patients on 100 mg/day and increase the dose gradually to attempt to lower the risk of mobilization flares. Achieving full therapeutic benefit, including a reduction in flares, frequently requires doses greater than the commonly used 300 mg/day.17 The serum urate level should be monitored every 2 weeks during dose escalation until the level is less than 6 mg/dL. Once a stable level is established, the serum urate can be checked once or twice a year to ensure that therapeutic concentrations are maintained.

The rare but potentially fatal hypersensitivity syndrome is a concern with allopurinol. If a rash develops in a patient taking allopurinol, the drug should be discontinued, as rash can be a precursor of severe systemic hypersensitivity.

Renal function must be considered in allopurinol dosing, and treatment should always be initiated at lower doses in patients with renal disease.18 However, recent reports indicate that allopurinol doses can be gradually and safely increased to an effective level that achieves a serum urate concentration of less than 6 mg/dL even in patients with reduced kidney function.19,20

Uricosurics

The uricosuric agent probenecid works by increasing the urinary excretion of urate.10 Probenecid is commonly dosed at 500 mg twice daily, with a maximum daily dose of 2 g, in an attempt to reach the target serum urate level. Probenecid is unlikely to be effective if the patient’s serum creatinine is greater than 2 mg/dL.21

When a uricosuric agent is used, a 24-hour urine urate measurement must be taken to identify and exclude urate overproducers (patients with more than 800 to 1,000 mg of uric acid in a good 24-hour collection), as such patients are at risk for uric acid kidney stones. Additionally, aspirin interferes with probenecid’s effect on the renal tubules. The ideal candidate for uricosuric therapy has good kidney function, is not a urate overproducer, and is willing to drink 8 glasses of water a day to minimize the risk of kidney stones (Table 2).

Evidence supporting urate targets and continuous maintenance of urate reductions

If a serum urate level of less than 6 mg/dL is achieved and maintained, gout flares will be reduced and crystals can be depleted from inside the joint.22–25 Additionally, the size of tophi can be reduced and their recurrence prevented.26–28 Serum urate levels below 4 mg/dL can result in more rapid dissolution of tophi.26

Reprinted, with permission, from Journal of Rheumatology (Bull PW, Scott JT. J Rheumatol 1989; 16:1246–1248).
Figure 1. Frequency of acute gout flares in a randomized trial of patients with gout who received allopurinol either continuously (left) or on an intermittent basis (right).29
Urate-lowering therapy with allopurinol or probenecid is generally a lifelong commitment. Intermittent therapy or cessation of therapy can lead to recurrent attacks.21,28,29 In a randomized trial examining outcomes of continuous versus intermittent urate-lowering therapy with allopurinol, gout attacks were eliminated after about 2 years of therapy in patients who continuously received allopurinol, whereas they continued to recur beyond 2 years in patients who received allopurinol intermittently (ie, due to the way it was prescribed or nonadherence) (Figure 1).29

Patient commitment and education are essential

No treatment plan will succeed without the commitment of the patient, so discussion to determine the patient’s willingness to commit to lifetime therapy is warranted. A number of surveys have shown that the rate of continued use of allopurinol after it is initially prescribed is less than 50%.17 If the physician or nurse monitors adherence, however, treatment is more likely to be successful.30

Patients need more education about gout, as education may improve adherence and treatment success. Patient education material is available from the Arthritis Foundation (www.arthritis.org/disease-center.php) and the Gout & Uric Acid Education Society (www.gouteducation.org).

CONCLUSION

A comprehensive treatment strategy is critical to ensure ideal gout therapy. Acute flares should be addressed as rapidly as possible with an anti-inflammatory agent selected on the basis of the patient’s comorbidities and other medications. Most patients require chronic urate-lowering therapy to deplete crystals from joints and prevent flares. Initiation of urate-lowering therapy should be considered early in the disease course, following resolution of the acute attack. Low-dose anti-inflammatory prophylaxis should be initiated when any urate-lowering therapy is started. Regular monitoring of serum urate will ensure effective dosing to achieve a target serum urate level of less than 6 mg/dL. Once urate deposits are depleted, acute flares should cease.

ADVERTISEMENT
ADVERTISEMENT
ADVERTISEMENT