Updates in uricase therapy for gout

Urate-lowering therapy (ULT) plays a pivotal role in treating gout patients. Unfortunately, some patients receiving oral ULT fail to achieve the target serum urate levels of < 6.8 mg/dl, the solubility level of uric acid. Exogenous uricases, considered "enzyme replacement therapy," are a therapeutic option for patients with uncontrolled gout in whom oral ULT has not been efficacious, is not tolerated, or is contraindicated, in some due to underlying comorbidities. Currently, two uricases are available: pegloticase and rasburicase. Pegloticase is indicated for treating uncontrolled gout, while rasburicase is used to prevent tumor lysis syndrome.

The main limitations of pegloticase include gout flares and infusion reactions, which are linked to the formation of antidrug antibodies. Immunomodulation and anti-inflammatory prophylaxis can help reduce these issues. New PEGylated uricases, including nanoencapsulated sirolimus combined with pegadricase (NASP) and PRX-115, are being developed and may offer improved options.

Exogenous uricases available and those under development are discussed, focusing on immunomodulation and anti-inflammatory prophylaxis to reduce flares, prevent antidrug antibody formation and infusion reactions, and mitigate loss of efficacy in patients with uncontrolled gout needing uricase replacement therapy.