PegloticaseRx

Trade Names: Krystexxa

Class: Urate-oxidase enzyme; pegylated recombinant uricase; antigout agent

Preparations: 8 mg/ml for i.v.  infusion

Dose: 8 mg every two weeks by slow i.v. infusion over at least 120 minutes

Indications: Chronic symptomatic gout refractory to conventional therapy

Mechanism of Action: A recombinant urate-oxidase that converts uric acid to allantoin

Contraindications: G-6PD deficiency, hypersensitivity

Precautions: Screen for G-6PD. Anaphylaxis and infusion reactions occur, administer under close supervision in a health care facility with ability to treat these.  Premedicate with antihistamine and corticosteroid. Infusion reactions can be delayed – observe patient for 1-2 hours after infusion. Risk of infusion reaction with first and subsequent infusions; with subsequent infusions risk is greater in patients whose uric acid is more than 6 mg/dL.  Delayed hypersensitivity reactions can occur. Monitor uric acid before repeat infusions and  consider discontinuing treatment if uric acid more than 6 mg/dL (likely indicates high-titre antibodies). Treatment causes  gout flares – prophylaxis should be used.

Pregnancy Risk: C

Monitoring: Monitor uric acid level before next infusion; usually decreases to less than 1 mg/dL. A lack of response after an initial response usually means that anti-pegloticase antibodies have formed and an increased risk of severe allergy.

Adverse Effects
Common: Infusion  reactions (26%), formation of anti-pegloticase antibodies (90%), rash, pruritus, nausea, gout flare (40-67% even with colchicine or NSAID treatment)
Less common: Anaphylaxis (6.5%), exacerbation of heart failure

Drug Interactions
Urate lowering therapies including allopurinol and febuxostat should be discontinued prior to the use of pegloticase and should not be initiated during  pegloticase therapy.

Patient Instructions: Allergy is common and can be serious; gout flares are common

Comments: An extremely expensive but very effective therapy usually reserved for patients with tophaceous gout  refractory to conventional therapy. Tophi can decrease in size rapidly. Acute attacks of gout are frequent. Serious allergy is a problem. Optimal duration of therapy and safety of a repeated course after a drug-free interval are not defined.

Clinical Pharmacology: Rapid onset of action, marked reduction in uric acid within 24 hours; half-life 14 days

Cost: $$$$$

BIBLIOGRAPHY

Sundy JS, Baraf HS, Yood RA, et al Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment: two randomized controlled trials. JAMA 2011;306:711-20. PMID: 21846852.