The drug lesinurad in combination with febuxostat exhibited better results in lowering blood levels of urate than febuxostat alone in phase III clinical trial of 324 patients with tophaceous gout.

Gout results from the accumulation of urate crystals in the joints which produces inflammation and causes intense pain. There can be large deposits of urate crystals (tophi) form in some people which may cause chronic joint inflammation and damage. According to 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 first-line urate-lowering treatment consists of a xanthine oxidase inhibitor, either allopurinol or febuxostat, which inhibits urate production. However many patients are not able to attain  <5.0 mg/d level of urate through these drugs.
In the phase III clinical trial which involved 324 patients with tophaceous gout, the combination of the lesinurad drug with febuxostat was used. It showed that this combination as much better in lowering blood levels of urate compared to febuxostat alone. Over 12 months, significantly more patients in the combination group achieved target levels of urate than patients in the febuxostat group.

Lesinurad was able to inhibit the transporter of uric acid in the kidney and enhance their excretion in the urine. So combining lesinurad 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.