Pegloticase is a newer urate-lowering drug approved for refractory gout. Its mechanism and limitation compared to rasburicase include:
- A Pegloticase inhibits xanthine oxidase with higher potency than allopurinol; resistance develops via XO gene amplification
- B Pegloticase blocks renal URAT1 transporter with greater selectivity than lesinurad
- C Pegloticase is pegylated recombinant uricase that converts urate to allantoin; PEGylation extends half-life but neutralizing anti-drug antibodies develop in ~40% patients, causing loss of efficacy and infusion reactions ✓
- D Pegloticase is an oral agent that metabolizes urate via a non-enzymatic pathway unique to the liver
Correct answer: C. Pegloticase is pegylated recombinant uricase that converts urate to allantoin; PEGylation extends half-life but neutralizing anti-drug antibodies develop in ~40% patients, causing loss of efficacy and infusion reactions
Explanation
Pegloticase is a PEGylated porcine-baboon chimeric uricase that oxidizes uric acid to allantoin (highly soluble, easily excreted). Unlike rasburicase (non-pegylated, short half-life of 18 hours, for tumor lysis syndrome), pegloticase has a prolonged half-life (~2 weeks) due to PEGylation. However, neutralizing IgG antibodies against both the uricase and the PEG component develop in ~35–40% of patients, causing loss of efficacy and hypersensitivity/infusion reactions. Monitoring urate levels predicts antibody development — rising urate suggests loss of effect.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.