Refractory gout: what is it and what to do about it?

The purpose of this review is to discuss the defining characteristics of refractory gout and the pharmacological management of this problem. Refractory gout refers to those patients who have ongoing symptoms of active disease and cannot maintain a target serum urate less than 6 mg/dl. Patients with refractory gout have reduced quality of life, functional impairment, and joint destruction. Multiple factors contribute to refractory gout, and they often relate to delayed or insufficient dosing with allopurinol. Chronic kidney disease imparts a dose limitation on allopurinol that further impairs the effectiveness of urate-lowering therapy. Febuxostat, a novel xanthine oxidase inhibitor, represents a potential alternative to allopurinol in refractory gout patients. Uricase, the enzyme that catalyzes conversion of uric acid into allantoin, is showing promise with its ability to rapidly diminish serum urate levels. The recently defined role of the NALP3 inflammasome in the inflammatory phase of gout suggests a potential role for interleukin-1 inhibition in urate crystal-induced inflammation. Refractory gout occurs when urate levels are not adequately controlled. Emerging therapies may improve the clinical course of patients with recalcitrant disease.