To apropriately manage gout, it is important to distinguish between treatment of acute gout attacks and management of the underlying metabolic defect. While acute attacks are treated with anti-inflammatory agents, the underlying hyperuricemia must be addressed by lowering the serum urate concentration to levels that lead to prevention of acute flares, together with consideration of the contributing role of the patient’s lifestyle factors and comorbidities. This article surveys treatment options for both acute gout attacks and the underlying hyperuricemic state, focusing on considerations to guide therapy selection and optimize prospects for treatment success.
ACUTE GOUTY ARTHRITIS: ANTI-INFLAMMATORY AGENTS AND KEY ISSUES FOR THEIR USE
One of the most important considerations in selecting an anti-inflammatory medication is how the patient’s comorbidities, such as renal disease, or concurrent medications may influence the choice of agent, as outlined in Table 1.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
A number of NSAIDs are available to treat acute flares of gout.1–3 When used at a full anti-inflammatory dose, all NSAIDs appear to be equally effective.
NSAIDs must be used cautiously in patients who have any of a number of comorbid conditions, as detailed in Table 1. If a patient is otherwise healthy—without significant renal, cardiovascular, or gastrointestinal disease—and has no history of aspirin allergy, NSAIDs are the treatment of choice for acute gout attacks. Use of a proton pump inhibitor can improve gastrointestinal tolerance of NSAIDs and reduce the likelihood of gastric bleeding but may not avoid other concerns. Indomethacin can cause headache or even confusion, particularly in the elderly.
Colchicine can be an effective alternative for acute therapy.4,5 If a patient with previously documented gout can be coached to begin colchicine at the first hint of a gout attack, a full-blown attack often can be prevented. A colchicine regimen of 0.5 or 0.6 mg 3 times daily, although not well studied, may be effective while limiting the diarrhea, nausea, and vomiting that is predictable with hourly colchicine dosing.6,7 Colchicine must be used cautiously in patients with renal or liver disease and is contraindicated in patients undergoing dialysis.8
Systemic corticosteroids are often used for polyarticular gout or in patients with contraindications to NSAIDs or colchicine.9 When they are used in diabetic patients, glycemic control must be monitored, and an increased insulin dose can be prescribed temporarily until glucose levels normalize.
Corticosteroids may also be injected directly into the joint, as this approach offers reduced risks compared with oral administration. Direct injection is especially useful in patients with attacks that involve only one or two joints.
TREATING THE UNDERLYING HYPERURICEMIA THROUGH URATE-LOWERING STRATEGIES
Terminating the acute flare manages gout symptoms but does not treat the underlying disease. Crystals often remain in the joint after flares have resolved. Addressing the underlying metabolic condition requires lowering serum urate levels, which can deplete crystals and reduce or prevent gout flares.
The goals of urate-lowering therapy are to reduce serum urate levels to less than 6 mg/dL in order to mobilize and deplete crystals with minimal toxicity.10
Role of lifestyle interventions
As discussed by Weaver earlier in this supplement, obesity and certain patterns of food and alcohol consumption can increase the risk of developing hyperuricemia and gout. In addition to weight loss, dietary changes.such as reducing intake of animal purines, high-fructose sweeteners, and alcohol, and increasing intake of vitamin C or bing cherries.may lower serum urate levels modestly (ie, by 1 or 2 mg/dL).11–15 While lifestyle interventions may be all that is needed in some patients with early mild gout, such interventions generally do not replace the need for urate-lowering drug therapy in cases of existing gout. Accordingly, this discussion focuses on medications used to treat hyperuricemia in the United States: the xanthine oxidase inhibitor allopurinol and the uricosuric agent probenecid.
Initiating urate-lowering drug therapy
Chronic therapy should be discussed with the patient early in the course of the disease. Treatment recommendations need to be individualized based on the patient’s overall health, comorbidities, and willingness to adhere to chronic treatment.
Initiation of urate-lowering therapy is appropriate to consider after the acute attack has fully resolved and the patient has been stable for 1 to 2 weeks. If a patient’s serum urate level is very high (eg, > 10 mg/dL), urate-lowering therapy may be initiated even after a single attack, as progression is more likely to occur with higher levels. Treatment should be initiated long before tophi or persistent joint damage develop. If the patient already has objective radiographic evidence of gouty changes in the joints, or if tophi or nephrolithiasis are present when the patient is first seen, urate-lowering therapy should be started.
Concurrent low-dose anti-inflammatory prophylaxis
Abrupt decreases (or increases) in serum urate levels may precipitate gout flares. For this reason, anti-inflammatory prophylaxis should be used when urate-lowering therapy is initiated, as it can quickly reduce serum urate levels. Colchicine (0.6 mg once or twice daily)8 or NSAIDs (eg, naproxen 250 mg/day) prescribed at lower than full anti-inflammatory doses may be used to prevent flares in this setting. When using long-term colchicine in a patient with renal disease, lower doses must be used and the patient should be monitored closely for reversible axonal neuromyopathy and vacuolar myopathy or rhabdomyolysis; the latter complication may be more frequent in patients taking concurrent statin or macrolide therapy. There are no controlled studies on the benefits and safety of prophylactic NSAID use in gouty patients with comorbidities.
Borstad et al documented in a placebo-controlled study that colchicine prophylaxis at the time of allopurinol initiation reduces flares but does not completely abolish them.16 From 0 to 3 months after therapy initiation, the mean number of flares was 0.57 in patients who received colchicine versus 1.91 in patients who received placebo (P = .022); from 3 to 6 months after initiation, the mean number of flares was 0 versus 1.05 in the respective patient groups (P = .033).16
Depending on the body’s urate load, it may take many months to deplete crystals. There is evidence that prophylaxis should be used for at least 3 to 6 months to reduce the risk of mobilization flares.16 Patients should be warned during this time that gout flares may still occur and should be treated promptly. Prophylaxis should continue longer in patients with tophi, often until the tophi have resolved.