What is the best approach to manage stubborn gout?

From the Guidelines

Managing stubborn gout requires a comprehensive approach that prioritizes urate-lowering therapy, lifestyle modifications, and preventive strategies to reduce morbidity, mortality, and improve quality of life. The most recent and highest quality study, the 2020 American College of Rheumatology guideline for the management of gout 1, recommends a multifaceted approach to managing gout. For acute gout flares, NSAIDs like indomethacin or colchicine are first-line treatments, while corticosteroids like prednisone may be used for those who cannot take these medications.

Long-term Management

For long-term management, urate-lowering therapy is essential, with allopurinol or febuxostat being the primary options, as recommended by the 2012 American College of Rheumatology guidelines for management of gout 1. The goal is to maintain serum uric acid levels below 6 mg/dL. Pegloticase may be considered for severe cases unresponsive to standard treatments.

Lifestyle Modifications

Lifestyle modifications are crucial and include:

• Limiting purine-rich foods (red meat, seafood, beer)
• Maintaining a healthy weight
• Staying hydrated
• Reducing alcohol consumption
• Regular exercise
• Encouraging low-fat dairy products, as recommended by the 2016 updated EULAR evidence-based recommendations for the management of gout 1

Monitoring and Adjustment

Regular monitoring of uric acid levels and kidney function is necessary to adjust medication dosages. These approaches work by either reducing inflammation during acute attacks or lowering uric acid production/increasing excretion to prevent crystal formation in joints. The primary objective is to reduce serum uric acid levels to prevent gout flares and improve quality of life, as emphasized by the 2020 American College of Rheumatology guideline 1.

From the FDA Drug Label

The dosage of allopurinol tablets to accomplish full control of gout and to lower serum uric acid to normal or near-normal levels varies with the severity of the disease. The minimal effective dosage is 100 to 200 mg daily and the maximal recommended dosage is 800 mg daily To reduce the possibility of flare-up of acute gouty attacks, it is recommended that the patient start with a low dose of allopurinol tablets (100 mg daily) and increase at weekly intervals by 100 mg until a serum uric acid level of 6 mg/dL or less is attained but without exceeding the maximal recommended dosage. By selecting the appropriate dosage and, in certain patients, using uricosuric agents concurrently, it is possible to reduce serum uric acid to normal or, if desired, to as low as 2 to 3 mg/dL and keep it there indefinitely Gout flares may occur after initiation of KRYSTEXXA An increase in gout flares is frequently observed upon initiation of anti-hyperuricemic therapy, due to changing serum uric acid levels resulting in mobilization of urate from tissue deposits Gout flare prophylaxis with a non-steroidal anti-inflammatory drug (NSAID) or colchicine is recommended starting at least 1 week before initiation of KRYSTEXXA therapy and lasting at least 6 months, unless medically contraindicated or not tolerated.

The best approach to manage stubborn gout is to:

• Start with a low dose of allopurinol (100 mg daily) and increase at weekly intervals by 100 mg until a serum uric acid level of 6 mg/dL or less is attained but without exceeding the maximal recommended dosage of 800 mg daily 2
• Use uricosuric agents concurrently, if necessary, to reduce serum uric acid to normal or to as low as 2 to 3 mg/dL and keep it there indefinitely 2
• Provide gout flare prophylaxis with a non-steroidal anti-inflammatory drug (NSAID) or colchicine starting at least 1 week before initiation of KRYSTEXXA therapy and lasting at least 6 months, unless medically contraindicated or not tolerated 3 Key considerations include:
• Monitoring serum uric acid levels to determine the effectiveness of treatment and adjust the dosage as needed 2
• Managing gout flares concurrently as appropriate for the individual patient 3

From the Research

Managing Stubborn Gout

To manage stubborn gout, several approaches can be considered:

• Treating acute gout attacks with non-steroidal anti-inflammatory drugs (NSAIDs), colchicine, or corticosteroids 4, 5, 6
• Lowering excess stores of uric acid to prevent flares of gouty arthritis and to prevent tissue deposition of urate using urate-lowering therapies such as allopurinol, febuxostat, or probenecid 4, 5, 6
• Providing prophylaxis to prevent acute flares, which can be achieved through the use of colchicine or NSAIDs, although the optimal agent, dose, and duration for gout prophylaxis are unknown and require further investigation 5, 6

Urate-Lowering Therapies

Urate-lowering therapies are essential for the long-term management of gout:

• Allopurinol is an effective treatment for reducing concentrations of uric acid and is considered a first-line treatment for patients with gout 4, 5, 6
• Febuxostat is another xanthine oxidase inhibitor that is clinically equivalent to allopurinol 4
• Probenecid is a uricosuric drug that increases uric acid excretion and can be used as an alternative to allopurinol or febuxostat 4, 5

Special Considerations

In certain patient populations, such as those with cardiovascular disease or heart failure, special considerations must be taken into account:

• Colchicine is considered safe and potentially reduces the risk of myocardial infarction in patients with cardiovascular disease or heart failure 7
• Allopurinol and probenecid are considered first-line treatments for patients with cardiovascular disease or heart failure due to their safety and potential for reducing cardiovascular outcomes 7
• Nonsteroidal anti-inflammatory drugs should be avoided in patients with cardiovascular disease or heart failure due to the increased risk of adverse cardiovascular events 7

Treatment in the Elderly

In elderly patients, extreme caution is necessary when prescribing treatments for gout:

• NSAIDs with short plasma half-life are preferred, but should be avoided in patients with peptic ulcer disease, renal failure, uncontrolled hypertension, or cardiac failure 8
• Colchicine is poorly tolerated in the elderly and is best avoided 8
• Allopurinol is the urate-lowering drug of choice, but its use in the aged is associated with an increased incidence of both cutaneous and severe hypersensitivity reactions, and the dose must be kept low 8