For gout patients with suboptimal responses to the standard-of-care therapy allopurinol, researchers found that combining lesinurad with allopurinol significantly reduced serum urate levels to less than 6.0 mg/dl. This combination therapy is a promising new treatment for gout patients needing further urate-lowering therapy.
The study appears in the December 28 online issue of Arthritis & Rheumatology.
This study was a phase III, randomized, double-blinded, placebo-controlled trial conducted with 603 patients (ages 22-81) over 12 months. Patients with gout were randomized to receive lesinurad 200 mg, lesinurad 400 mg, or a placebo in a 1:1:1 ratio. All patients continued taking their pre-study dosage of allopurinol, which ranged from 300-800 mg/day.
Led by Kenneth Saag, M.D., from the University of Alabama at Birmingham, the research team evaluated the efficacy of daily lesinurad in addition to allopurinol, compared to a placebo plus allopurinol option in patients with serum urate levels ≥6.0mg/dl. The primary outcome was the percentage of patients achieving serum urate levels of <6.0mg/dl. Secondary outcomes included the mean rate of gout flare-ups needing treatment and the proportion of patients achieving complete resolution of ≥1 target tophus.
There were significant improvements for patients taking lesinurad plus allopurinol compared to patients taking allopurinol alone. In particular, the 400 mg lesinurad plus allopurinol group had the highest proportion of patients (59.2%) achieving a serum urate level of <6.0mg/dl, followed by the 200 mg lesinurad plus allopurinol group, which had 54.2% of patients achieving a serum urate level of 6.0mg/dl.
In contrast, the proportion of patients achieving a serum urate level of 6.0mg/dl was 27.9 percent in the allopurinol alone group.
With regard to secondary outcomes, lesinurad plus allopurinol was not found to be superior to allopurinol alone for gout flares-ups and complete resolution of tophi.
Gout is managed through drug therapy and/or lifestyle management. Allopurinol is the standard of care and recommended first-line urate-lowering therapy for gout patients, with a maximum daily dose of 800 mg. In previous clinical trials of allopurinol, more than half of patients did not reach target serum urate levels of <6.0 mg/dl with the commonly prescribed dose of 300 mg/day. In clinical practice, when serum urate targets are not achieved with allopurinol, a substitute therapy or combination therapy that includes allopurinol is recommended.
Lesinurad is a novel selective uric acid reabsorption inhibitor that, when combined with allopurinol, increases urinary excretion of uric acid and reduces production of urate.
Previous studies assessing lesinurad combined with allopurinol have shown significant reductions in serum urate levels. However, these studies have been phase I and phase II clinical trials. This is one of the first known phase III studies to evaluate the efficacy of lesinurad plus allopurinol in a large sample of gout patients.
“Lesinurad was generally well tolerated, particularly at the 200-mg dose, where the AE profile was comparable to that of allopurinol alone. The majority of TEAEs were grade 1 or 2, and the proportions of patients with serious adverse events and TEAEs leading to study withdrawal were comparable across treatment groups,” wrote Dr. Saag and colleagues.
This research was supported by Ardea Biosciences, Inc., a member of the AstraZeneca group.
Kenneth G. Saag, David Fitz-Patrick, Jeff Kopicko, et al. “Lesinurad Combined With Allopurinol: A Randomized, Double-Blind, Placebo-Controlled Study in Gout Patients With an Inadequate Response to Standard-of-Care Allopurinol (a US-Based Study),” Arthritis & Rheumatology. Published online December 28, 2016. DOI: 10.1002/art.39840.