Reduction of plasma urate levels following treatment with multiple doses of pegloticase (polyethylene glycol-conjugated uricase) in patients with treatment-failure gout - Results of a phase II randomized study

Objective. To assess the efficacy of pegloticase in achieving and maintaining plasma urate levels of <6 mg/dl in gout patients in whom other treatments have failed, and to assess the pharmacokinetics and safety of pegloticase. Methods. Forty-one patients were randomized to undergo 12-14 weeks of treatment with pegloticase at I of 4 dosage levels: 4 mg every 2 weeks, 8 mg every 2 weeks, 8 mg every 4 weeks, or 12 mg every 4 weeks. Plasma uricase activity, plasma urate, and antipegloticase antibodies were measured, pharmacokinetic parameters were assessed, and adverse events were recorded. Results. The mean plasma urate level was reduced to <= 6 mg/dl within 6 hours in all dosage groups, and this was sustained throughout the treatment period in the 8 mg and 12 mg dosage groups. The most effective dosage was 8 mg every 2 weeks. Twenty-six patients received all protocol doses. The percentage of the patients in whom the primary efficacy end point (plasma urate <6 mg/dl for 80% of the study period) was achieved ranged from 50% to 88%. Gout flares occurred in 88% of the patients. The majority of adverse events (excluding gout flare) were unrelated to treatment and were mild or moderate in severity. Infusion-day adverse events were the most common reason for study withdrawal (12 of 15 withdrawals). There were no anaphylactic reactions. Antipegloticase antibody, present in 31 of 41 patients, was associated with reduced circulating half-life of pegloticase in some patients. Conclusion. Pegloticase, administered in multiple doses, was effective in rapidly reducing and maintaining plasma urate levels at <= 6 mg/dl in most patients in whom conventional therapy had been unsuccessful due to lack of response, intolerability, or contraindication.