From the Guidelines
Long-term management of gout should prioritize urate-lowering therapy (ULT) with allopurinol as the first-line medication, started at a low dose and titrated to achieve a serum uric acid level below 6 mg/dL, as recommended by the 2020 American College of Rheumatology guideline 1.
Key Components of Gout Management
- Urate-lowering therapy (ULT) is the cornerstone of treatment, with allopurinol being the preferred first-line medication, as supported by the 2020 American College of Rheumatology guideline 1
- Initiation of ULT should be accompanied by prophylaxis against acute flares for at least 3-6 months using colchicine, nonsteroidal anti-inflammatory drugs, or glucocorticoids, as recommended by the 2020 American College of Rheumatology guideline 1
- Lifestyle modifications, including weight loss, adequate hydration, limited purine-rich foods, reduced alcohol consumption, and avoidance of high-fructose corn syrup, are essential for ongoing management, as emphasized by the EULAR evidence-based recommendations for gout 1
Medication and Dosing
- Allopurinol should be started at a low dose (≤100 mg/day) and titrated up to achieve a serum uric acid level below 6 mg/dL, as recommended by the 2020 American College of Rheumatology guideline 1
- Febuxostat (≤40 mg/day) is an effective alternative for patients who cannot tolerate allopurinol, as supported by the 2020 American College of Rheumatology guideline 1
- Colchicine (0.6mg once or twice daily) or low-dose NSAIDs can be used for prophylaxis against acute flares, as recommended by the EULAR evidence-based recommendations for gout 1
Monitoring and Follow-up
- Regular monitoring of serum uric acid levels every 2-5 weeks during dose titration and then every 6 months once at target is necessary to ensure treatment efficacy, as emphasized by the 2020 American College of Rheumatology guideline 1
- ULT is typically lifelong, and discontinuation often leads to recurrence of gout attacks, highlighting the importance of long-term management, as supported by the EULAR evidence-based recommendations for gout 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 average is 200 to 300 mg/day for patients with mild gout and 400 to 600 mg/day for those with moderately severe tophaceous gout 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 While adjusting the dosage of allopurinol tablets in patients who are being treated with colchicine and/or anti-inflammatory agents, it is wise to continue the latter therapy until serum uric acid has been normalized and there has been freedom from acute gouty attacks for several months
The management of gout long term involves:
- Dosing: The dosage of allopurinol varies with the severity of the disease, with an average of 200 to 300 mg/day for mild gout and 400 to 600 mg/day for moderately severe tophaceous gout.
- Titration: Starting with a low dose of 100 mg daily and increasing at weekly intervals by 100 mg until a serum uric acid level of 6 mg/dL or less is attained.
- Concurrent therapy: Using uricosuric agents concurrently to reduce serum uric acid to normal or as low as 2 to 3 mg/dL.
- Monitoring: Continuing colchicine and/or anti-inflammatory agents until serum uric acid has been normalized and there has been freedom from acute gouty attacks for several months.
- Maintenance: Maintaining a daily urinary output of at least 2 liters and a neutral or slightly alkaline urine to prevent renal precipitation of urates.
- Adjustments: Adjusting the dose of allopurinol based on serum uric acid levels and renal function. 2
From the Research
Long-term Management of Gout
- The primary goal of long-term management of gout is to achieve and maintain serum urate levels in a subsaturating range 3.
- Lifestyle modifications are crucial in the long-term management of gout, including:
- Weight loss
- Avoidance of alcohol
- Avoidance of purine-rich foods
- Avoidance of diuretics 4
- Urate-lowering therapies (ULT) are indicated in patients with:
- ULT agents include:
- The target serum uric acid (SUA) level for most patients is below 6 mg/dL, but a lower target of less than 5 mg/dL is recommended for patients with tophi 4, 6
- Febuxostat has been shown to be effective in achieving target SUA levels, especially in patients with renal dysfunction, and may be considered as a first-line treatment option 6
- However, febuxostat is associated with an increased risk of all-cause and cardiovascular mortality, and its use should be carefully considered 5
Urate-Lowering Therapies
- Allopurinol is the most commonly used ULT agent, but it carries a risk of inducing severe cutaneous adverse reactions, especially in patients with chronic kidney disease and those harboring the HLA-B*5801 allele 4
- Febuxostat is a suitable alternative to allopurinol, with established efficacy and safety in a high number of clinical studies 6
- Probenecid is another ULT agent, but its use is less common due to limited availability and efficacy data 4, 6