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OBJECTIVE: To evaluate the short-term safety and outcome of 2 different experimental applications of rasburicase 0.2 mg/kg (monthly vs daily) in patients with tophaceous gout not treatable by allopurinol. Rasburicase could be useful for patients with gout that is unresponsive to allopurinol or who cannot tolerate the therapy. METHODS: Five patients received 6 monthly infusions of rasburicase (Group 1) and 5 received 5 daily infusions (Group 2). RESULTS: In Group 1, serum uric acid (SUA) level decreased significantly, from 612.6 +/- 162.4 micromol/l at baseline to 341.2 +/- 91.8 micromol/l after 6 infusions (p = 0.001). Changes in tophus area were observed in 2 patients. In Group 2, daily infusions produced a rapid, marked decrease in SUA level during treatment. Yet SUA levels measured at 1 month (511.5 +/- 128.4 micromol/l) and 2 months (572 +/- 96.2 micromol/l) after treatment were not significantly lower than at baseline (573.6 +/- 48.2 micromol/l). No patient from Group 2 showed reduced tophus size. Eight of 10 patients experienced an adverse event, the most common being gout flare despite prophylactic treatment with colchicine. CONCLUSION: Monthly infusions of rasburicase appear to be a possible therapy for severe gout not treatable by other means. Tolerance of rasburicase in gout appears to be diminished by frequent triggering of gout attacks, and hypersensitivity reactions might be an important limitation to longterm therapy.