What are the management options for Gout (Gouty Arthritis)?

From the Guidelines

Gout management should prioritize a treat-to-target approach with urate-lowering therapy (ULT), lifestyle modifications, and anti-inflammatory prophylaxis to minimize morbidity, mortality, and improve quality of life.

Key Recommendations

• For acute gout attacks, NSAIDs like naproxen (500mg twice daily) or indomethacin (50mg three times daily) for 3-5 days are first-line treatments, as recommended by the American College of Physicians 1.
• Colchicine is also effective when started early (1.2mg initially, followed by 0.6mg one hour later, then 0.6mg once or twice daily until symptoms resolve) 1.
• For long-term management, lifestyle modifications are crucial, including weight loss if overweight, limiting alcohol (especially beer), avoiding high-purine foods like organ meats and shellfish, and staying well-hydrated 1.
• Urate-lowering therapy is indicated for patients with frequent attacks, tophi, joint damage, or kidney stones, with allopurinol (starting at 100mg daily and gradually increasing to achieve target uric acid levels below 6mg/dL) as the most common option, and febuxostat as an alternative 1.
• Prophylaxis with low-dose colchicine (0.6mg daily) or NSAIDs during the first 3-6 months of urate-lowering therapy helps prevent flares as uric acid levels change 1.

Rationale

The 2020 American College of Rheumatology guideline for the management of gout 1 provides the most recent and highest quality evidence for gout management, emphasizing a treat-to-target approach with ULT, lifestyle modifications, and anti-inflammatory prophylaxis. Regular monitoring of uric acid levels and kidney function is essential for effective long-term management, as recommended by the American College of Rheumatology 1 and the American College of Physicians 1. By prioritizing a treat-to-target approach with ULT, lifestyle modifications, and anti-inflammatory prophylaxis, healthcare providers can minimize morbidity, mortality, and improve quality of life for patients with gout.

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.

Gout Management with Allopurinol:

• The dosage of allopurinol varies with the severity of the disease, with an average of 200-300 mg/day for mild gout and 400-600 mg/day for moderately severe tophaceous gout.
• The recommended starting dose is 100 mg daily, increasing by 100 mg at weekly intervals until a serum uric acid level of 6 mg/dL or less is attained.
• The maximal recommended dosage is 800 mg daily.
• It is recommended to start with a low dose and increase gradually to reduce the possibility of flare-up of acute gouty attacks 2.
• Indomethacin can be used to relieve the pain, reduce the fever, swelling, redness, and tenderness of acute gouty arthritis 3.

From the Research

Gout Management Overview

• Gout is a common form of acute inflammatory arthritis caused by the deposition of monosodium urate crystals within the synovium of joints, leading to severe pain and reduced quality of life 4.
• The condition is characterized by swelling, pain, or tenderness in a peripheral joint or bursa, including the development of a tophus 5.

Treatment of Gout Flares

• Standard pharmacotherapies for gout flares include colchicine, NSAIDs, and oral or intramuscular corticosteroids, with IL-1 inhibitors as an option for flare refractory to standard therapies 4, 6.
• Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat acute gout, with low-certainty evidence suggesting they may improve pain at 24 hours and have little to no effect on function, inflammation, or adverse events 7.
• Glucocorticoids and NSAIDs are probably equally beneficial in terms of pain relief, improvement in function, and treatment success, although NSAIDs probably result in more total adverse events 7.

Urate-Lowering Therapy

• Urate-lowering therapies aim to prevent gout flares, with an emphasis on a treat-to-target strategy; the escalation of therapies until the target serum uric acid is reached 4.
• Initial treatments include allopurinol and febuxostat, with uricosuric agents, probenecid, sulfinpyrazone, and benzbromarone, as adjuncts 4, 8.
• Allopurinol is an agent of first choice for urate-lowering therapy, but screening for HLA*B58:01 mutation is recommended in certain populations to decrease the occurrence of allopurinol hypersensitivity syndrome 6.
• Febuxostat is another efficacious urate-lowering therapy, but has received a U.S. FDA black box warning for cardiovascular safety 6.

Emerging Therapies

• Novel therapies, including IL-1β antagonists and uricosuric agents, are being developed for the treatment of gout 4, 6.
• Pegloticase is effective for patients with recalcitrant gout, but its immunogenicity significantly threatens the achievement of sustained urate-lowering responses 6.