Add-on lesinurad helps lower serum urate in gout patients uncontrolled on febuxostat
The addition of lesinurad to febuxostat appears to provide superior serum urate (sUA)-lowering benefit compared with febuxostat alone, with acceptable safety profile and clinically significant effect on tophi, in patients with tophaceous gout requiring additional therapy, according to the results of a 12-month, phase III trial.
A total of 324 patients (mean age 54.1 years; 95.4 percent male) with sUA ≥8.0 mg/dl (≥6.0 mg/dl on urate-lowering therapy) and ≥1 measurable target tophus were randomized to receive lesinurad (200 or 400mg daily) or placebo as add-on to febuxostat, which was initiated at a once-daily dose of 80 mg 3 weeks prior to randomization.
The respective primary and secondary endpoints were the proportion of patients achieving sUA <5.0 mg/dl at month 6 and the proportion of those with complete resolution of ≥1 target tophus at month 12. Percent change in total target tophi area was also evaluated. Assessments were performed at baseline, week 2 and months 1 to 6, 8, 10, and 12 for sUA and every 3 months for tophi.
The proportion of patients achieving sUA target by month 6 was significantly greater with lesinurad 400 mg vs placebo (76.1 vs 46.8 percent; p<0.0001). No significant difference was observed between lesinurad 200 mg and placebo (56.6 vs 46.8 percent; p=0.13). At all other time points, significantly more patients in the lesinurad 200 mg arm achieved the sUA target.
Complete tophus resolution was comparable among the treatment groups. However, reductions in total target tophi area was significantly greater with lesinurad (200 and 400 mg) than with placebo (50.1 and 52.9 percent vs 28.3 percent; p<0.05).
Lesinurad plus febuxostat demonstrated a safety profile that was generally comparable with febuxostat alone, except for higher rates of predominately reversible serum creatinine elevation, particularly with the 400 mg dose.
Lesinurad 200 mg is a novel selective uric acid reabsorption inhibitor approved for treatment of gout in combination with a xanthine oxidase inhibitor (XOI) in patients who do not achieve target sUA levels on an XOI alone, researchers said.
“Combination therapy with lesinurad and febuxostat provides a dual mechanism, addressing both uric acid excretion and urate production, and may represent a treatment option for patients with tophaceous gout on febuxostat who warrant additional therapy,” they added.