What are the treatment options for refractory gout (gouty arthritis)?

From the Guidelines

Refractory gout should be managed with a multi-faceted approach, starting with maximizing the dose of first-line medications like allopurinol or febuxostat, and considering combination therapy with uricosuric agents or pegloticase in severe cases, as recommended by the 2016 updated EULAR evidence-based recommendations for the management of gout 1.

Treatment Options

The treatment of refractory gout involves several options, including:

• Maximizing the dose of first-line medications like allopurinol (up to 800 mg daily) or febuxostat (up to 120 mg daily) 2
• Combination therapy with uricosuric agents such as probenecid (500-1000 mg twice daily) or lesinurad (200 mg daily) added to xanthine oxidase inhibitors 2
• Pegloticase (8 mg IV every two weeks) for severe cases, which enzymatically converts uric acid to allantoin 1 ### Prophylaxis and Lifestyle Modifications During treatment intensification, prophylaxis against flares with:
• Colchicine (0.6 mg once or twice daily) 3
• Low-dose NSAIDs
• Low-dose prednisone (5-10 mg daily) should be continued for 3-6 months Lifestyle modifications, including:
• Weight loss if appropriate
• Avoidance of alcohol (especially beer and spirits) and sugar-sweetened drinks
• Heavy meals and excessive intake of meat and seafood should be avoided
• Low-fat dairy products should be encouraged
• Regular exercise should be advised 3 ### Monitoring and Adjustments Medication adherence should be emphasized and serum uric acid levels monitored regularly to guide therapy adjustments 2. The goal is to maintain serum uric acid levels at <6 mg/dL (360 mmol/L) and <5 mg/dL (300 mmol/L) in those with severe gout 1.

From the FDA Drug Label

General An increase in acute attacks of gout has been reported during the early stages of administration of allopurinol tablets, even when normal or subnormal serum uric acid levels have been attained. The use of colchicine or anti-inflammatory agents may be required to suppress gouty attacks in some cases In patients with severely impaired renal function or decreased urate clearance, the half-life of oxipurinol in the plasma is greatly prolonged. INDICATIONS AND USAGE Probenecid tablets are indicated for the treatment of the hyperuricemia associated with gout and gouty arthritis.

• Treatment options for refractory gout (gouty arthritis) include:
  • Allopurinol tablets, with a recommended initial dose of 100 mg daily, increasing at weekly intervals by 100 mg until a serum uric acid level of 6 mg/dL or less is attained
  • Colchicine or anti-inflammatory agents to suppress gouty attacks
  • Probenecid tablets to treat hyperuricemia associated with gout and gouty arthritis
• Key considerations:
  • Patients with decreased renal function require lower doses of allopurinol tablets
  • Patients with severely impaired renal function or decreased urate clearance may require a dose of 100 mg per day or 300 mg twice a week, or perhaps less, of allopurinol tablets 4
  • Probenecid tablets can be used as an adjuvant to therapy with certain antibiotics 5

From the Research

Treatment Options for Refractory Gout

The treatment options for refractory gout, also known as gouty arthritis, include:

• Urate-lowering therapy (ULT) with xanthine oxidase inhibitors (XOIs) such as allopurinol and febuxostat 6, 7, 8, 9, 10
• Febuxostat is recommended as a first-line ULT for treating gout in the 2012 American College of Rheumatology Guidelines 7
• Allopurinol is the most frequently prescribed agent for gout in the United States, but most patients treated with allopurinol do not achieve target serum uric acid (sUA) levels 6

Comparison of Allopurinol and Febuxostat

• Febuxostat is more effective than allopurinol in achieving target sUA levels, with 42.2% of patients achieving goal sUA levels compared to 29.2% of allopurinol-treated patients 7
• Febuxostat has a faster onset of action and is more likely to achieve sUA concentrations less than 6 mg/dl compared to allopurinol 6
• Allopurinol has a higher risk of discontinuation due to poor health literacy, and patients with tophi and shorter symptom duration are at high risk for poor persistence of XOIs 10

Factors Affecting Treatment Outcomes

• Patient adherence to ULT is a significant contributor to poor patient outcomes, and poor adherence is prevalent 9
• Factors contributing to poor adherence include physician and patient characteristics, and interventions such as initiation of prophylactic anti-inflammatory medication, frequent follow-ups, and regular serum urate monitoring can improve adherence 9
• The presence of tophi and symptom duration < 24 months are independently associated with a higher risk of XOI withdrawal 10

Dosage and Administration

• The recommended starting dose of febuxostat is 40 mg/day, which may be increased to 80 mg/day after 2 weeks if patients do not achieve sUA levels less than 6 mg/dl 6
• Dosage adjustment in mild-to-moderate renal insufficiency is unnecessary, but data are lacking on the safety of febuxostat in patients with severe renal impairment 6