Therapeutic perspectives on uricases for gout.

Available recombinant uricases (rasburicase, pegloticase) are potent hypouricaemic agents for tophaceous gout, but their long-term use is in question. We have performed a literature review on uricases, using Scirus, PubMed, Science Direct, and several other search engines. We have also consulted the records of drug regulatory authorities and patents on uricases. Rasburicase (Fasturtec(®)) was approved in Europe for tumour lysis syndrome induced by chemotherapy, in a single daily infusion dose for a maximum of 7 days. A retrospective study (n=10) conducted in patients with gout and three clinical cases have shown that infusions spaced over time, over several months, ensure the control of serum uric acid and help to eliminate or significantly reduce the size of tophi. However, repeated gout attacks (despite colchicine) and hypersensitivity reactions (despite corticosteroids) have dampened enthusiasm for its use in gout. Pegloticase was recently approved by the Food and Drug Administration (FDA) for patients with chronic gout, refractory or intolerant to conventional hypouricaemic therapy. A 6 month study versus placebo showed that pegloticase (infused at 8 mg every 2 weeks), induced a significant decrease in plasma uric acid in about 40% of patients (associated with a tendency for tophi dissolution). However, the remaining patients were non-responders, which correlated with the formation of pegloticase antibodies and infusion reactions. Research efforts are needed to develop less immunogenic uricases. In conclusion, some uricases could have an important role in the treatment of gout, for instance as a first-line treatment and over a short period of several months in patients with severe and tophaceous gout to allow rapid tophi dissolution.