The drug lesinurad in combination with febuxostat was better at lowering blood levels of urate than febuxostat alone in a phase III clinical trial of 324 patients with tophaceous gout. Over 12 months, significantly more patients in the combination group achieved target levels of urate than patients in the febuxostat group.
Gout occurs when urate crystals accumulate in the joints, causing inflammation and intense pain. In some people, large deposits of urate crystals (tophi) form. These deposits can cause chronic joint inflammation and damage. Current guidelines for long-term treatment of gout recommend urate-lowering therapy to maintain a blood urate level below 5.0 mg/dl in patients with tophaceous gout. The recommended first-line urate-lowering therapy is a xanthine oxidase inhibitor, either allopurinol or febuxostat, which inhibits urate production. Many patients are unable to achieve a urate level of <5.0 mg/dl with these drugs, however.
Lesinurad inhibits a uric acid transporter in the kidney and increases excretion of uric acid in the urine. Therefore, lesinurad in combination with a xanthine oxidase inhibitor provides a dual mechanism of action to lower blood levels of urate by increasing kidney excretion of uric acid and reducing urate production.
"Combination treatment of lesinurad and febuxostat represents a new therapeutic option for patients with severe gout who cannot achieve the serum urate treatment target with xanthine oxidase inhibitor monotherapy," said Prof. Nicola Dalbeth, lead author of the Arthritis & Rheumatology trial.
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Nicola Dalbeth et al. Lesinurad, a Selective Uric Acid Reabsorption Inhibitor, in Combination With Febuxostat in Patients With Tophaceous Gout: A Phase III Clinical Trial, Arthritis & Rheumatology (2017). DOI: 10.1002/art.40159