What are the next steps for treating gout that is not responding to prednisone?

From the Guidelines

For gout that is not responding to prednisone, consider switching to colchicine (0.6 mg once or twice daily) or an NSAID like indomethacin (50 mg three times daily for acute flares) if not contraindicated, as recommended by the 2020 American College of Rheumatology guideline for the management of gout 1. Alternatively, use interleukin-1 inhibitors such as anakinra (100 mg subcutaneously daily for 3-5 days) for severe cases. For long-term management, start urate-lowering therapy with allopurinol (starting at 100 mg daily, gradually increasing) or febuxostat (40-80 mg daily) once the acute flare resolves, as suggested by the 2012 American College of Rheumatology guidelines for management of gout 1. Target serum uric acid levels below 6 mg/dL, as recommended by the 2016 updated EULAR evidence-based recommendations for the management of gout 1. Prophylactic colchicine (0.6 mg daily) or low-dose NSAIDs should be used when initiating urate-lowering therapy to prevent flares, as recommended by the 2020 American College of Rheumatology guideline for the management of gout 1. Lifestyle modifications are also important, including:

• Weight loss if overweight
• Limiting alcohol (especially beer)
• Avoiding high-purine foods
• Staying well-hydrated These approaches work by either reducing inflammation through different pathways than steroids or by addressing the underlying cause of gout by lowering uric acid levels, which prevents crystal formation in joints. Key considerations in managing gout include patient education on diet, lifestyle, treatment objectives, and management of comorbidities, as well as the use of xanthine oxidase inhibitor therapy with either allopurinol or febuxostat as the first line pharmacologic urate-lowering therapy approach, as outlined in the 2012 American College of Rheumatology guidelines for management of gout 1. It is essential to monitor serum urate levels and adjust treatment accordingly to achieve the target level, and to consider combination oral urate-lowering therapy or pegloticase for patients with severe gout disease burden and refractoriness to, or intolerance of, appropriately dosed oral urate-lowering therapy options, as recommended by the 2012 American College of Rheumatology guidelines for management of gout 1 and the 2020 American College of Rheumatology guideline for the management of gout 1.

From the FDA Drug Label

The use of colchicine or anti-inflammatory agents may be required to suppress gouty attacks in some cases The next steps for treating gout that is not responding to prednisone may include the use of colchicine or other anti-inflammatory agents to suppress gouty attacks.

• Allopurinol may also be considered as an alternative treatment option, but it is essential to carefully monitor the patient's response and adjust the dosage as needed 2.
• It is crucial to note that allopurinol may take several months to achieve control of acute attacks, and the patient should be closely observed during the early stages of administration 2.
• The patient's renal function should also be carefully monitored, especially if they have pre-existing renal disease or poor urate clearance 2 2.

From the Research

Next Steps for Treating Gout Not Responding to Prednisone

• If gout is not responding to prednisone, the next steps may involve exploring alternative treatment options, such as:
  • IL-1 inhibitors, including anakinra, rilonacept, and canakinumab, which have been shown to be effective in reducing pain and inflammation in acute gout attacks and preventing recurrent attacks 3
  • Novel uricosurics, such as verinurad and arhalofenate, which are being developed as potential treatments for gout 4
  • Pegloticase, which is effective for patients with recalcitrant gout, but may require immunomodulatory co-therapy to abrogate its immunogenicity 4
• It is also important to consider prophylaxis to prevent acute flares, which can be achieved with low-dose colchicine or low-dose NSAIDs, such as naproxen, for up to 6 months 5
• Lifestyle modifications, such as dietary changes and weight loss, may also be beneficial in preventing gout flares and reducing serum urate levels 6

Treatment Options for Acute Gout

• NSAIDs, colchicine, and glucocorticoids are commonly used to treat acute gout flares, but may not be effective for all patients 6
• IL-1β antagonists, such as canakinumab, may be effective for arresting flares, but their cost-effectiveness may limit their use as first-line therapy 4
• Intra-articular corticosteroids and adrenocorticotropic hormone (ACTH) may also be used to treat acute gout flares, but their use is generally reserved for severe cases or when other treatments are contraindicated 6

Urate-Lowering Therapy

• Allopurinol and febuxostat are commonly used to lower serum urate levels, but may not be effective for all patients 6
• Pegloticase may be effective for patients with recalcitrant gout, but requires careful monitoring due to its immunogenicity 4
• Novel uricosurics, such as verinurad and arhalofenate, may offer alternative treatment options for patients who are intolerant of or refractory to existing therapies 4