What are the dosing recommendations and contraindications for pegloticase (uricase-like enzyme) in patients with severe gout?

Pegloticase Dosing and Contraindications for Severe Gout

Pegloticase is indicated only for patients with severe, debilitating chronic tophaceous gout who have failed or cannot tolerate conventional urate-lowering therapies, with a recommended dose of 8 mg intravenously every 2 weeks. 1, 2

Indications

• Pegloticase should be reserved for patients with crystal-proven severe debilitating chronic tophaceous gout and poor quality of life, in whom the serum uric acid (SUA) target cannot be reached with any other available drug at maximal dosage (including combinations) 2
• It is specifically indicated for chronic gout refractory to conventional therapy, defined as patients who have failed to normalize serum uric acid and whose signs and symptoms are inadequately controlled with xanthine oxidase inhibitors at maximum appropriate doses 1
• Pegloticase is not recommended as first-line urate-lowering therapy for any gout scenario 2
• It is not recommended for the treatment of asymptomatic hyperuricemia 1

Dosing Recommendations

• The standard dose is 8 mg administered as an intravenous infusion every 2 weeks 1
• The infusion must be administered over no less than 120 minutes via gravity feed, syringe-type pump, or infusion pump 1
• Do not administer as an intravenous push or bolus 1
• Discontinue oral urate-lowering agents before starting pegloticase 1

Administration Requirements

• Pegloticase should be administered in healthcare settings by healthcare providers prepared to manage anaphylaxis and infusion reactions 1
• Patients must be pre-medicated with antihistamines and corticosteroids before each infusion 1, 3
• Monitor serum uric acid levels before each infusion and consider discontinuing treatment if levels increase to above 6 mg/dL, particularly when 2 consecutive levels above 6 mg/dL are observed 1

Contraindications

• Glucose-6-phosphate dehydrogenase (G6PD) deficiency: Patients at higher risk (e.g., those of African and Mediterranean ancestry) should be screened before starting pegloticase due to the risk of hemolysis and methemoglobinemia 1
• Pegloticase should not be combined with other urate-lowering therapies as this may mask increases in serum uric acid levels that warn of increased risk of infusion reactions and anaphylaxis 2
• Caution is advised in patients with congestive heart failure, as exacerbation was reported in 2% of patients receiving pegloticase in clinical trials 4

Monitoring and Safety Considerations

• Monitor serum uric acid levels before each infusion 1
• Patients should be closely monitored for signs of anaphylaxis and infusion reactions during and after administration 1
• Anaphylaxis may occur with any infusion (including first infusion) and generally manifests within 2 hours, though delayed hypersensitivity reactions have been reported 1
• The risk of infusion reactions is higher in patients who have lost therapeutic response (indicated by rising uric acid levels) 1
• Anti-pegloticase antibody formation is common (observed in 31 of 41 patients in one study) and may reduce the half-life and efficacy of pegloticase 5

Special Populations

• No dose adjustment is required for patients with renal impairment 1
• No dose adjustment is needed for patients 65 years of age and older 1
• Safety and effectiveness in pediatric patients less than 18 years of age have not been established 1

Treatment Duration

• There is no firm consensus on the appropriate duration of pegloticase therapy once symptoms and signs of gout have decreased, including reduction in size or resolution of tophi 2
• Some experts suggest considering a switch to oral urate-lowering therapy once all tophi have disappeared, if feasible 2

Emerging Strategies

• Recent research suggests that concomitant use of immunosuppressive agents like mycophenolate mofetil may reduce immunogenicity and prolong the efficacy of pegloticase, with 86% of patients maintaining target serum urate levels at 12 weeks compared to 40% with pegloticase alone 6

Pegloticase represents a powerful but specialized treatment option for severe gout that has not responded to conventional therapies, with significant efficacy but also important safety considerations that require careful patient selection and monitoring.