When is pegloticase (Pegloticase) preferred over allopurinol (Allopurinol) or febuxostat (Febuxostat) for treating gout?

From the Guidelines

Pegloticase is preferred over allopurinol or febuxostat in patients with severe, treatment-refractory gout who have failed to achieve target serum uric acid levels despite maximum doses of oral urate-lowering therapies. This typically includes patients with tophaceous gout, frequent flares, and uric acid levels that remain above 6 mg/dL despite appropriate doses of allopurinol (up to 800 mg daily) or febuxostat (up to 80 mg daily) 1.

Key Considerations

• Pegloticase is administered as an intravenous infusion of 8 mg every two weeks and works by converting uric acid to allantoin, which is more water-soluble and easily excreted by the kidneys.
• It's particularly effective for rapidly reducing urate crystal burden in patients with extensive tophi.
• However, pegloticase has important limitations: it carries a high risk of infusion reactions (particularly in patients who develop anti-drug antibodies), requires regular IV administration, and is significantly more expensive than oral options.
• Patients should be pre-medicated with antihistamines and corticosteroids before each infusion to reduce reaction risk, and serum uric acid levels should be monitored before each dose, as loss of efficacy may indicate antibody development and increased risk of reactions.

Clinical Guidelines

• The 2012 American College of Rheumatology guidelines recommend pegloticase as an appropriate option for patients with severe gout disease burden and refractoriness to, or intolerance of, appropriately dosed oral ULT therapy options 1.
• The guidelines also recommend attempting upwards dose titration of one xanthine oxidase inhibitor (XOI) to the respective maximum appropriate dose, and considering combination oral ULT with one XOI agent and one uricosuric agent when the serum urate target has not been met by appropriate dosing of an XOI 1.

Patient Selection

• Patients with severe, treatment-refractory gout who have failed to achieve target serum uric acid levels despite maximum doses of oral urate-lowering therapies are the primary candidates for pegloticase therapy.
• These patients typically have tophaceous gout, frequent flares, and uric acid levels that remain above 6 mg/dL despite appropriate doses of allopurinol or febuxostat.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Pegloticase Preference Over Allopurinol or Febuxostat

Pegloticase is preferred over allopurinol or febuxostat for treating gout in the following situations:

• In patients with refractory chronic gout who are intolerant to or unresponsive to urate-lowering therapies 2, 3, 4
• When conventional urate-lowering drugs such as allopurinol and febuxostat are not effective in managing gout symptoms 2, 3
• In cases where patients have chronic refractory gout and have failed to achieve treatment goals with conventional agents 3

Key Considerations

Some key considerations when using pegloticase include:

• Immunogenicity to pegloticase is associated with loss of urate-lowering response and the risk of infusion reactions 2, 3, 4
• Pegloticase is effective in treating hyperuricemia and the clinical manifestations of gout in patients who cannot be adequately managed with conventional therapy 2, 3
• New dosing regimens and co-administration of immunosuppressive agents are being employed to overcome the limitation of immunogenicity and extend the benefits of pegloticase to a larger number of patients 3

Comparison with Other Urate-Lowering Therapies

Comparisons with other urate-lowering therapies have shown that:

• Febuxostat is more effective at lowering serum urate than allopurinol, especially in patients with renal dysfunction 5
• Pegloticase is associated with more withdrawals due to adverse events and infusion reactions compared to other urate-lowering therapies 6