Update on Gout and Hyperuricemia

J. F. Baker; H. Ralph Schumacher


Int J Clin Pract. 2010;64(3):371-377. 

In This Article

New Therapies

Acute Gout

The recent interest in the role of the NALP (NACHT, LRR and pyrin domain-containing protein) inflammasome, which generates interleuking (IL)-1β has suggested that this cytokine may be a target for therapy for inflammation associated with gout. An uncontrolled trial of IL-1 inhibition with anakinra was effective in the treatment of acute gout in 10 patients and may also have a role in treatment-resistant inflammation associated with tophaceous gout.[31,32] Another IL-1 inhibitory agent, rilonacept, has also been shown to be effective at suppressing flares of gouty arthritis and C-reactive protein (CRP) levels.[33] There are insufficient data to recommend the routine use of these expensive IL-1 inhibitory systemic therapies, although they may be considered in some refractory cases.

Chronic Hyperuricemia

Febuxostat, an oral non-purine selective inhibitor of xanthine oxidase, has recently been approved in the United States for the treatment of hyperuricemia in gout. The pharmacodynamics of febuxostat is not altered by moderate renal impairment and it has appeared safe in initial studies in those with mild to moderate renal impairment.[34]

Febuxostat, at a dose of 80–240 mg, was superior to standard dose allopurinol in reaching a SUA goal of < 6 mg/dl with similar rates of adverse events in patients with serum Cr < 2 mg/dl. This medication is approved at dosing of 40–80 mg, however, a greater percentage of patients were able to meet their goal SUA with doses as high as 240 mg without increased rates of adverse events.[34] The safety of febuxostat has not yet been assessed in those with severe renal impairment. With this caution, this medication is likely to be a useful adjunct to current therapies, especially in those who are unable to tolerate allopurinol.

Other agents that may lower the SUA level are under investigation. Pegylated recombinant mammalian uricase (PEG-uricase) has been shown to be effective in a phase two trials at lowering SUA and preventing subsequent flares of gout.[35–37] This advance may play a role in the management of some patients with difficult to manage tophaceous gout.

Losartan, fenofibrate, statins, vitamin C and increased coffee intake have all been shown to modestly increase urine uric acid excretion.[38–41] There are currently no data in regard to the clinical utility of these interventions alone in the treatment of hyperuricemia and gout. However, consideration of hyperuricemia when choosing between blood pressure and cholesterol treatments may be appropriate and helpful in many patients. Similarly, increasing coffee (> 4 cups daily) and vitamin C consumption in the diet might be recommended for those patients with the modest hyperuricemia who are resistant to medication, however, the benefits of these interventions are likely to be small compared with other pharmacological interventions.