Critical appraisal of the role of pegloticase in the management of gout

Gout is a debilitating disease secondary to chronic hyperuricemia, and the subsequent deposition of monosodium urate crystals is responsible for acute flare, gout arthropathies, tophi and renal lithiasis. Uric acid is the end product of purine metabolism in humans because the gene encoding uricase was lost during hominoid evolution. Pegloticase is a recombinant mammalian uricase conjugated to polyethylene glycol that catalyzes the oxidation of uric acid into allantoin, a more soluble end product. The use of this drug as urate-lowering therapy is a new approach in treating severe gout refractory to conventional therapy with xanthine oxidase inhibitors and uricosuric agents. Intravenous pegloticase has potent and long-lasting urate-lowering capacity with rapid efficacy on tophi resolution. However, pegloticase treatment is associated with infusion-related reactions despite prevention therapy with high-dose corticosteroids. Exacerbation of pre-existing cardiovascular diseases is another concern. The mechanisms of these events are unknown. Caution with long-term use of pegloticase is warranted, especially for patients with cardiovascular diseases.