BARCELONA, Spain—Gout is one of the few kinds of arthritis for which a cure is routinely possible, but two thirds of patients with diagnosed hyperuricemia are not receiving urate-lowering therapy (ULT), and the rest are mostly being treated with inadequate doses of allopurinol, Michael Doherty, MD, explained at the 2007 EULAR meeting.¹ Dr. Doherty is professor of rheumatology at Nottingham University, in the UK.

"A key objective of long-term management of gout is ‘cure.' This is achieved by maintaining tissue urate levels below the saturation point for crystal formation, equivalent to a serum uric acid (SUA) of <360 µmol/L or <6mg/dL, thus dissolving existing crystals and preventing further crystal formation. The lower the SUA is below the saturation point, the faster the depletion of urate crystals," Dr. Doherty writes. He suggests the main message for clinicians is that current treatments are used suboptimally. "The best way to affect most of the gout patients in your area is to better use the tools we already have," Dr. Doherty said.

Although a number of new drugs for treating gout are available or on the horizon, the purine xanthine oxidase inhibitor allopurinol (Zyloprim®, Lopurin®, Purinol®) remains the mainstay of treatment. However, Dr. Doherty said that only about one third of patients who might benefit from ULT receive allopurinol, generally at a dose of 300 mg although the typical approved use allows doses up to 800 mg and that only a minority of the patients treated with allopurinol have blood tests to monitor the adequacy of therapy. "Our problem is undertreatment, not overdosing of allopurinol," he said. The drug's principal drawback is allopurinol hypersensitivity syndrome, which occurs in about 1 of 1000 patients treated and is more common in patients with renal impairment.

Newer approaches to long-term management of gout include:

• Uricosurics, such as sulphinpyrazone, probenecid, and benzbromarone, have limited availability and are contraindicated in renal impairment. Dr. Doherty said that benzbromarone is effective in moderate impairment but can cause severe hepatotoxicity.
  
• Febuxostat, a nonpurine xanthine oxidase inhibitor that is more selective than allopurinol and will be available shortly in Europe. Dr. Doherty said that it has good efficacy when compared with 300 mg/day of allopurinol and it has not been associated with severe adverse events. Because of the speed with which febuxostat lowers serum uric acid levels, it risks triggering acute flares. Febuxostat should be used routinely with colchicine prophylaxis when initiating therapy.
  
• Uricase is a urate oxidase enzyme that humans (and some other primates) lack; it converts uric acid to allantoin. "When given intravenously, uricase reduces SUA to nearly zero. It is therefore given with steroids as prophylaxis of polyarticular attacks. There are reports of dramatic reductions in tophi using this agent, but at present immunogenicity limits its repeated use. A pegylated form of uricase is licensed for tumor lysis syndrome and there are current efforts to develop this enzyme for repeated use in gout, Dr. Doherty notes.
  
• Losartan and fenofibrate cause 20% to 40% reductions in SUA by increasing elimination of uric acid, but carry the risk of causing formation of uric acid crystals in the kidney in patients with renal impairment. Dr. Doherty advised considering losartan as an adjunctive agent in gout patients who also need treatment for hypertension or hyperlipidemia.
  
• Vitamin C doses of 500 mg/day can reduce SUA in hyperuricemic patients by about 20%.

For management of acute attacks of gout, Dr. Doherty recommended aspiration and steroid injections in accessible joints, parenteral or oral steroids, ACTH, colchicine, oral NSAIDs or coxibs, along with cold packs. IL-1 inhibitors and TNF-inhibitors are currently of theoretical interest.

Dr. Doherty emphasized the importance of patient education of gout management in modifiable factors such as diet, hypertension, hyperlipidemia, and especially obesity. He stressed the importance of patients' avoiding beer, because of its high guanosine content.

"You don't have to be teetotaler. In fact, you shouldn't be. One glass of red wine has definite health benefits. But we need to help and encourage gout patients to make lifestyle modifications that are permanent, such as changing the diet to include less red meat. Weight reduction is central and will not only reduce SUA levels but also improve comorbidities, especially metabolic syndrome," Dr. Doherty said. "Education concerning the principles of long-term gout management applying just existing treatment options would have a major impact on improving the outcome of this common inflammatory arthritis."

E-mail any comments to .

Reference

1. Doherty M. New therapies for gout. Presented at: EULAR 2007 Meeting; June 13-16, 2007; Barcelona, Spain. Abstract SP0073.