Pegloticase

PEGLOTICASE

Pegloticase is the newest urate-lowering therapy; it was approved by the FDA in September 2010 for the treatment of refractory chronic gout.

Chemistry

Pegloticase is a recombinant mammalian uricase that is covalently attached to methoxy polyethylene glycol (mPEG) to prolong the circulating half-life and diminish immunogenic response.

Pharmacokinetics

Pegloticase is a rapidly acting intravenous drug, achieving a peak decline in uric acid level within 24–72 hours. The serum half-life ranges from 6.4 to 13.8 days. Several studies have shown earlier clearance of PEG-uricase (mean of 11 days) due to antibody response when compared to PEG-uricase antibody-negative subjects (mean of 16.1 days).

Pharmacodynamics

Urate oxidase enzyme, absent in humans and some higher pri-mates, converts uric acid to allantoin. This product is highly solu-ble and can be easily eliminated by kidney. Pegloticase has been shown to maintain low urate levels for up to 21 days at doses of 4–12 mg, allowing for IV dosing every 2 weeks.

Adverse Effects

The most common adverse events include infusion reactions and gout flare (especially during the first 3 months of treatment). Nephrolithiasis, arthralgia, muscle spasm, headache, anemia, and nausea may occur. Other less frequent side effects noted include upper respiratory tract infection, peripheral edema, urinary tract infection, and diarrhea. There is some concern for hemolytic ane-mia in patients with glucose-6-phosphate dehydrogenase because of the formation of hydrogen peroxide by uricase; therefore, peg-loticase should be avoided in these patients. Large numbers of patients show immune responses to pegloticase. The presence of antibody is associated with shortened circulating half-life, loss of response leading to a rise in plasma urate levels, and a higher rate of infusion reactions. Monitoring of plasma uric acid level, with rising level as an indicator of antibody production, allows for safer administration and monitoring of efficacy.

Dosage

The recommended dose for pegloticase is 8 mg IV every 2 weeks. As noted for other urate-lowering therapy, patients should be started on prophylaxis for acute gout flares (using colchicine) while initiating pegloticase.