For the first time since allopurinol [Zyloprim] was introduced in 1964, the medical management of chronic gout may soon include new treatment options. The xanthine oxidase inhibitor febuxostat is expected to be approved by the Food and Drug Administration some time this year. There are also promising results of early clinical trials with recombinant, pegylated uricase, an enzyme that destroys uric acid in most nonhuman species.
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In addition, two cardiovascular drugs–the cholesterol-lowering agent fenofibrate (TriCor) and the angiotensin II receptor blocker losartan (Cozaar)–have been found to lower uric acid levels, unlike other drugs in their respective classes; urate is lowered by about 20% with fenofibrate and by a range of 3%-30% with losartan. Neither is FDA approved for gout, and although most experts would like to see more data on their use in gout, they believe these drugs may have ancillary value in hyperlipemic and/or hypertensive gouty patients.
These developments are coming at an opportune time. The population is aging and gaining weight, two of the main risk factors for gout, so physicians are likely to see more and more cases of gout in their offices in the coming years.
Most gout guidelines recommend lifestyle changes–especially weight loss and avoiding overindulgence in alcohol (primarily beer) or in foods rich in purine or fructose–as the first step in managing early gout. Antihyperuricemic medication is reserved for patients who do not respond to lifestyle changes and have recurrent gout attacks, develop tophi, or pass renal calculi containing uric acid. Some guidelines use uric acid excretion rates to help with that choice: A xanthine oxidase inhibitor, such as allopurinol, is recommended for those excreting more than 800 mg/24 hr, and uricosuric agents are recommended for those with lower rates. Other guidelines recommend screening for overexcretion using a “spot urine technique,” a measurement derived from the excretion rate of uric acid divided by the creatinine clearance (J. Rheumatol. 2001;28:1207-10). Uricosuric agents do not work and should not be used in overproducers (the minority of gout patients), whose kidneys are already eliminating uric acid at maximum capacity.
Many rheumatologists practice differently, however. Some offer a patient the option of starting chronic drug therapy after the first attack, before the patient makes lifestyle changes and any tests are performed. Their rationale is that 60% of patients with a first attack will have a second within a year and that any attack, even the first, can result in some joint damage. Many rheumatologists also prefer to use allopurinol first because it is effective in both overproducers and under-excreters; its once-daily dosing is easier than the dosing of a uricosuric; and it tends to be more reliable.
Studies consistently show that the goal of therapy should be to reduce serum urate levels to less than 6 mg/dL for the best chance of reducing gouty attacks and tophaceous deposits. Lesser reductions may slow or arrest disease progression but will not dissolve existing urate crystals.
Most rheumatologists stress that when urate-lowering therapy is instituted, patients must also be treated with low-dose colchicine prophylactic therapy–0.6 mg orally twice daily for patients who have intact renal function, with dose adjustments for patients who have renal dysfunction, for the elderly, and for those who develop GI intolerance–to reduce the likelihood of flare. They recommend that colchicine prophylaxis continue until the urate level has stabilized at the target level and the patient has not had an acute gouty attack for 3-6 months. Patients who cannot tolerate daily colchicine can be treated instead with an NSAID (50 mg of indomethacin twice daily or 250 mg of naproxen twice daily), although NSAIDs should be used with caution in patients with impaired renal function.
Urate-lowering therapy is never started during an active gout phase because of the risk of a flare and worsening arthritis; treatment should not be stopped in a patient already on a urate-lowering drug who is having an acute attack. Once begun, treatment is continuous, because intermittent therapy has been shown to be ineffective.
The elderly generally require dose adjustment of the drugs listed below.
Elizabeth Mechcatie, editor
Timothy F. Kirn, writer