Sundy JS et al. (2008) 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. Arthritis Rheum 58: 2882–2891

Gout patients who do not attain target serum urate levels of ≤6 mg/dl with conventional urate-lowering therapies are defined as having treatment-refractory gout. A proposed new therapy, urate oxidase (pegloticase), converts poorly soluble urate to allantoin, which is highly soluble and easily excreted. Following successful single-dose trials, Sundy and colleagues' phase II trial has demonstrated that multiple pegloticase infusions are effective in reducing and maintaining plasma urate at or below target levels in patients with treatment-refractory gout.

This open-label, parallel-group study included 41 patients from 9 US centers who had hyperuricemia and treatment-refractory gout or contraindications to conventional therapy (mean disease duration 14.4 years). Participants were randomly allocated to one of four 12–14-week pegloticase infusion regimens, which all showed statistically similar efficacy in achieving target plasma urate levels. This treatment did not prevent flare. Infusion-associated adverse events motivated 12 of 15 withdrawals from the study, so the protocol was amended from pegloticase administration in 100 ml phosphate-buffered saline over 30 min to 200 ml over 1 h.

The study demonstrated that pegloticase might be immunogenic at doses low enough to avoid accumulation, which suggests that its efficacy would decrease rapidly. Long-term, placebo-controlled trials including larger numbers of patients are required to determine the optimal pegloticase regimen, durability of response to pegloticase, adverse event rate and this treatment's potential to reduce clinical manifestations of gout.