Lesinurad in Combo With Febuxostat in Patients With Tophaceous Gout

Title: Lesinurad, a Selective Uric Acid Reabsorption Inhibitor, in Combination With Febuxostat in Patients With Tophaceous Gout: A Phase III Clinical Trial

Dalbeth, N et al.


What You Need to Know:

In patients with tophaceous gout, combination therapy of lesinurad plus febuxostat is more effective at reducing serum urate (sUA) levels as well as total target tophi area compared to febuxostat monotherapy.

Trial Design:

  • Randomized, placebo-controlled, phase 3 study evaluated the safety and efficacy of lesinurad + febuxostat compared to febuxostat alone in patients with tophaceous gout
  • “Patients with serum urate (sUA) ≥8.0 mg/dL (≥6.0 mg/dl on urate-lowering therapy) and ≥1 measurable target tophus were given febuxostat 80mg daily for 3 weeks before randomization to lesinurad (200 or 400mg daily) or placebo added to febuxostat”
  • Primary endpoint: percent of patients attaining sUA <5.0 mg/dL at month 6
  • Secondary endpoint: percent of patients with resolution of ≥1 target tophus at month 12
  • Additional endpoints: change in percent of total target tophi area, safety assessments (adverse events, laboratory findings)

Key Outcomes:

  • 76.1% of patients receiving 400mg of lesinurad (P<0.0001) and 56.6% of patients receiving 200mg lesinurad (P=0.13) achieved sUA target by Month 6 vs 46.8% of patients receiving febuxostat alone
  • “At all other timepoints, significantly more patients in the lesinurad 200mg group achieved sUA target”
  • No difference in complete tophus resolution observed between groups
  • Total target tophi area was reduced in patients receiving 200mg and 400mg of lesinurad + febuxostat compared to febuxostat monotherapy (50.1% and 52.9% vs 28.3%, respectively; P<0.05)
  • Safety assessments were similar among groups, however higher rates of reversible serum creatinine elevation was observed in the lesinurad-treated groups