medwireNews: Results of the phase III LIGHT trial suggest that gout patients who are treated with lesinurad 400 mg experience a greater reduction in serum uric acid (sUA) levels than those given placebo, but at the cost of renal-related adverse events.
Therefore, “[l]esinurad should not be used as monotherapy in patients with gout due to renal complications,” say Anne-Kathrin Tausche (Technical University Dresden, Germany) and fellow researchers in Rheumatology.
The LIGHT (Lesinurad Monotherapy in Gout Subjects Intolerant to Xanthine Oxidase Inhibitors) investigators randomly assigned 214 patients from North America, Europe, Australasia, and South Africa who were unable to take a xanthine oxidase inhibitor (XOI) to receive oral lesinurad 400 mg once daily or placebo for 6 months in addition to gout flare prophylaxis for the first 5 months. Over 90% of patients were male, with a mean age of 54.4 years and gout duration of 11.2 years.
A significantly higher proportion of the 107 patients receiving lesinurad achieved sUA levels below 6.0 mg/dL at month 6 compared with the 107 in the placebo group, at 29.9% versus 1.9%, and mean sUA levels were consistently lower in the lesinurad group at each monthly visit over the treatment period.
However, the beneficial effect of lesinurad on sUA levels did not translate into a significantly decreased risk for gout flares, with 11.8% of patients in the lesinurad group and 14.6% of those in the placebo group receiving treatment for a flare during month 6, after the cessation of prophylaxis.
Treatment-emergent adverse events (TEAEs) occurred in 77.6% of patients receiving lesinurad and 65.4% of placebo-treated patients. Renal-related TEAEs were reported in 17.8% and 0%, respectively, and 4.7% of lesinurad-treated patients experienced a renal-related serious adverse event (SAE), including two patients with renal failure, two with acute renal failure, and one with renal impairment.
Serum creatinine elevations also occurred only among patients who were treated with lesinurad, with 24.3% experiencing 1.5-fold elevated levels from baseline.
Based on these safety data and subsequent discussions with regulatory authorities, participants from Germany, Canada, and the USA withdrew from the trial before completion of the planned 2-year extension phase of the study, and the trial was terminated early, explain the researchers.
“Due to the high incidence of serum creatinine elevations and renal-related AEs, including SAEs, observed in this study, an indication for the use of lesinurad 400 mg in patients with gout was not pursued for regulatory approval as either monotherapy or in combination with an XOI,” they write, noting that the 200 mg dose is approved for use together with XOIs.
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