Urate oxidase in the prophylaxis or treatment of hyperuricemia: The United States experience

Abstract

Nonrecombinant urate oxidase (Uricozyme ®, Sanofi-Synthélabo, Inc, Paris, France) is a highly effective uricolytic agent, but its use is associated with hypersensitivity reaction manifested mainly by bronchospasm in approximately 5% of patients. Recently, several multi-institutional studies have evaluated the efficacy and safety of a recombinant urate oxidase (rasburicase). In a phase I/II study, all 131 patients with newly diagnosed acute lymphoblastic leukemia (ALL) or stage III/IV non-Hodgkin's lymphoma (NHL) experienced rapidly decreased plasma uric acid concentrations after receiving recombinant urate oxidase. Serum creatinine levels also decreased significantly. Toxicity was negligible, and none of the patients required dialysis. In a phase III trial, children with newly diagnosed ALL or stage III/IV NHL were stratified and randomized to receive recombinant urate oxidase or allopurinol. Results showed that the 27 patients who received recombinant urate oxidase had a significantly lower plasma uric acid concentration and a more rapid decline in serum creatinine level than did the 25 who took allopurinol. One patient in the recombinant urate oxidase group had hemolysis of unknown cause, and one in the allopurinol group required hemofiltration for hyperphosphatemia. To further assess the safety profile of recombinant urate oxidase, the data on 245 patients (173 children and 72 adults) who received this agent in a compassionate-use program were reviewed retrospectively. The drug produced dramatic decreases in uric acid concentrations in all patients. Nine patients (four children and five adults) had mild adverse reactions that were drug-related or of unknown etiology. These data suggest that recombinant urate oxidase is safe and effective in the prophylaxis and treatment of hyperuricemia associated with malignancy or chemotherapy.