Pegloticase is used for refractory chronic gout in patients who fail allopurinol and febuxostat. Its mechanism and the key limitation of long-term therapy is:

• A Inhibits URAT1 transporter to prevent urate reabsorption; resistance by URAT1 upregulation
• B Inhibits xanthine oxidase by a different mechanism than allopurinol; limited by hepatotoxicity
• C Promotes renal urate excretion via OAT1/OAT3 activation; limited by hypercalciuria
• D Pegylated recombinant uricase converts urate to soluble allantoin; anti-drug antibodies neutralize pegloticase and increase infusion reactions over time ✓

Explanation

Pegloticase is a pegylated recombinant porcine-like uricase that catalyzes the oxidation of uric acid to allantoin, a highly soluble and readily excreted product (humans lack functional uricase unlike most mammals). It rapidly and dramatically lowers serum urate and dissolves tophi. The major limitation is immunogenicity: about 40% of patients develop anti-pegloticase IgG antibodies that neutralize the enzyme, causing loss of efficacy (serum urate rises above 6 mg/dL) and predisposing to infusion reactions. Serum urate monitoring before each infusion is mandatory; a rise above 6 mg/dL signals antibody formation and mandates discontinuation. Co-administration of immunosuppressants (methotrexate, mycophenolate) is used to reduce immunogenicity.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.