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Lesinurad – A Novel Treatment for Gout?

November 18 2014 3:54 PM ET via RheumReports RheumReports

In the late breaking abstract poster session today, Saag et al presented the results of the CLEAR 1 and 2 trials examining the use of lesinurad (LES) in combination with allopurinol for the treatment of gout.

How does LES work? URAT1 is a transporter in the renal tubular lumen that is responsible for the majority of the reabsorption of filtered uric acid. Remember that ~90% of all filtered uric acid is ultimately reabsorbed. Lesinurad is a selective uric acid reabsorption inhibitor (SURI) that inhibits URAT1 thereby preventing the reabsorption of uric acid.

CLEAR 1 (USA) and CLEAR 2 (12 countries) were identical, randomized, double-blind, placebo-controlled trials comparing LES 400 mg + allopurinol (ALLO), LES 200 mg + ALLO, and PBO + ALLO in 1,213 patients.

The primary endpoint was the proportion of patients with sUA <6.0 mg/dL (360 umoL/L) at month 6. Secondary endpoints (month 12) included the rate of gout flares and the proportion of patients having resolution of tophus.

The proportion of patients achieving the primary endpoint was 54-55% for LES 200, 59-67% for LES 400, and 23-28% for PBO. These findings were statistically significant for both doses of LES.

Disappointingly, the secondary endpoints were not met. There were no significant differences in gout flares or tophus reduction.

The most concerning safety endpoint was an increase in serum creatinine (sCr) >1.5 x baseline with LES vs. PBO. This finding was dose-related occurring in 6% of patients in the LES 200 arm and 15-16% in the LES 400 arm. The sCr returned to baseline in most patients (85-100% for LES 200 and 80% for LES 400).

In conclusion, lesinurad in combination with allopurinol may represent a future treatment option for patients with gout.


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Dr. Andy Thompson
Dr. Andy Thompson

Dr. Andy Thompson is an Associate Professor at Western University and founder of Rheuminfo.com, Rheumtalks.com, and RheumReports.com.

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