New Guidelines for the Treatment of Hyperuricemia, Gout

Gout results from an excess body burden of uric acid, with hyperuricemia variably defined as a serum urate level exceeding either 6.8 or 7.0 mg/dL. Tissue deposition of monosodium urate monohydrate crystals in supersaturated extracellular fluids of the joints and in certain other sites results in acute gouty arthritis, chronic arthritis, and renal disease.

The goal of the 2012 American College of Rheumatology (ACR) guidelines was to develop systematic nonpharmacologic and pharmacologic recommendations for effective treatments in gout with an acceptable risk/benefit ratio. Four specific areas of gout management covered by the guidelines were urate-lowering therapy (ULT), chronic gouty arthritis with tophaceous disease, analgesic and anti-inflammatory management of acute gouty arthritis, and pharmacologic anti-inflammatory prophylaxis of attacks of gouty arthritis.

The top recommendation is for more intensive education of patients on diet, lifestyle choices, treatment objectives, and management of concomitant diseases; this includes recommendations on specific dietary items to encourage, limit, and avoid.

"We provide a comorbidity check-list for the clinician that I expect will be very useful in day-to-day practice," Dr. Terkeltaub said. "We have also provided a cohesive set of diet and lifestyle recommendations. This has been a problem because of the fact and fiction mixed in to diet and lifestyle approaches to gout. The guideline is an advance because it provides a more actionable set of recommendations for physicians to talk about with their patients."

Table. Comorbidity Checklist for Patients With Gout

Obesity, dietary factors

Excessive alcohol intake

History of urolithiasis

Chronic kidney disease (CKD)

Potential genetic or acquired causes of uric acid overproduction (inborn error of purine metabolism, psoriasis, myeloproliferative or lymphoproliferative disease)

Lead intoxication

Dr. Terkeltaub added, "Many patients feel that diet and moderation alone should be sufficient to manage their gout. Diet is important, but what is really important is getting the serum urate to a target appropriate for that patient. At a bare minimum it should be less than 6 mg/dL. In clinical practice, the serum uric acid level is no longer part of the routine metabolic panel, but it is inexpensive and should be monitored regularly in gout patients."

Dr. Terkeltaub noted that dietary or alcohol excess can increase uric acid and trigger acute gout attacks in susceptible individuals, but he said that dietary restrictions alone may not reduce serum urate levels enough to prevent joint damage in gout patients.

"The average-age gout patient in our clinical trials has a serum uric acid level between 9.5 and 10 mg/dL. Even ideal diet and alcohol intake will likely lower that by only 10% to 15%, which will not bring the typical gout patient to a serum uric acid of 6 mg/dL. Often people need urate-lowering drugs to get them to the target level and keep them there. People feel that if they have fewer gout attacks, they are better, but the disease will progress unless serum uric acid is reduced to a level where deposits of urate crystals in the joint tissues will disappear," Dr. Terkeltaub said.

Start Low, Go Slow With Allopurinol

The ACR guidelines recommend treating patients with a xanthine oxidase inhibitor (XOI), such as allopurinol, as the first-line pharmacologic ULT approach. The recommended goal is to reduce serum urate to less than 6 mg/dL, and the initial allopurinol dosage should be no greater than 100 mg/day, the guidelines say. This should be followed by gradual increase of the maintenance dose, which can safely exceed 300 mg even in patients with CKD.

"Clinicians often start allopurinol at doses that are too high but maintain allopurinol at doses that are too low," Dr. Terkeltaub said. "We give specific guidance on start low, go slow dose escalation."

To avoid allopurinol toxicity, the guidelines recommend considering HLA-B*5801 prescreening of patients at particularly high risk for severe adverse reaction to allopurinol (eg, Koreans with stage 3 or worse kidney disease and all patients of Han Chinese and Thai descent).

For CTGA, the guidelines recommend combination therapy with 1 XOI (allopurinol or febuxostat) and 1 uricosuric agent when target urate levels are not achieved. They advise using probenecid as an alternative first-line urate-lowering drug in the setting of contraindication or intolerance to at least 1 XOI (except in patients with creatinine clearance below 50 mL/minute). They also recommend pegloticase in patients with severe gout disease who do not respond to standard, appropriately dosed ULT.

Acute Gout Requires Prompt Treatment

Part 2 of the guidelines covers therapy and prophylactic anti-inflammatory treatment for acute gouty arthritis. These guidelines recommend initiating pharmacologic therapy within 24 hours of onset of acute gouty arthritis attack while continuing urate-lower therapy without interruption.

Nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, or oral colchicine are the recommended first-line treatment for acute gout, and combinations of these medications can be used for severe or unresponsive cases.

To prevent the acute gout flares that may accompany the early stages of ULT, the guidelines recommend oral colchicine or low-dose NSAIDs as long as there is no medical contraindication or lack of tolerance.

Dr. Terkeltaub advised caution with colchicine dosing. "One of the major problems in quality of care is that people were getting drowned in colchicine for acute gout. We assessed the evidence and decided to go with the [US Food and Drug Administration]-approved regimen of low-dose colchicine for early acute gout flare. That is a major recommendation. When people get drowned in high doses of colchicine for a long time for acute gout, the rate of adverse events is quite high."

Resumes

• New guidelines from the ACR offer updated recommendations on the management of hyperuricemia.
• Patient education regarding diet, lifestyle, treatment objectives, and management of comorbid conditions is a core therapeutic measure for gout and for hyperuricemia.
• The first-line pharmacological ULT in gout is XOI therapy with either allopurinol or febuxostat.
• Target serum urate level should be lower than 6 mg/dL, and often lower than 5 mg/dL, to maintain improvements in gout signs and symptoms.
• The starting dosage of allopurinol should not exceed 100 mg/day (or less in moderate to severe CKD). This should be gradually titrated upward.
• Even in patients with CKD, the maintenance dose of allopurinol can exceed 300 mg daily.
• Before starting allopurinol, rapid polymerase chain reaction–based HLA-B*5801 screening should be considered for subpopulations with elevated HLA-B*5801 allele frequency and with high risk for severe allopurinol hypersensitivity in HLA-B*5801-positive patients.
• These high-risk groups include Koreans with stage 3 or worse CKD and all persons of Han Chinese and Thai descent.
• When appropriate dosing of an XOI does not achieve the serum urate target, combination oral ULT with 1 XOI agent and 1 uricosuric agent is recommended.
• For patients with severe gout disease burden and lack of response to or intolerance of appropriately dosed oral ULT, pegloticase may be used.
• Updated recommendations for the management of acute gouty arthritis were also presented.
• Pharmacotherapy should be started within 24 hours of onset of an acute gouty arthritis attack.
• During an acute attack of gout, established pharmacologic ULT should be continued without interruption.
• Appropriate first-line therapy for acute gout includes NSAIDs, corticosteroids, or oral colchicine.
• For severe or refractory attacks, certain combinations of these drugs may be used.
• All patients with gout who are starting to receive ULT should receive pharmacologic anti-inflammatory prophylaxis.
• This should be continued if there is any clinical evidence of continuing gout disease activity and/or the serum urate target has not yet been reached.
• Except for patients with a lack of tolerance or medical contraindications, oral colchicine is an appropriate first-line choice for prophylaxis of gout attack and may be used with appropriate dose adjustment in patients with CKD or drug interactions.
• Except for patients with a lack of tolerance or medical contraindications, low-dose NSAIDs are appropriate for first-line prophylaxis of gout attack.

CLINICAL IMPLICATIONS

• According to the 2012 ACR guidelines, core therapy for management of gout and for hyperuricemia includes patient education about diet, lifestyle, treatment objectives, and management of comorbid conditions. First-line pharmacological ULT in gout is XOI therapy with either allopurinol or febuxostat to achieve a target serum urate level of less than 6 mg/dL, and often less than 5 mg/dL.
• For an acute gouty arthritis attack, pharmacotherapy with NSAIDs, corticosteroids, or oral colchicine should be started within 24 hours of onset, and ULT should be continued without interruption. All patients with gout starting ULT should receive pharmacologic anti-inflammatory prophylaxis with oral colchicine or low-dose NSAIDs.

references:

1. http://www.medscape.org/viewarticle/773669: New Guidelines for the Treatment of Hyperuricemia, Gout