Background & Objectives
When treating hyperuricemia in patients with gout, the goal is to lower and maintain serum urate levels to <6.0 mg/dL in the average patient and <5.0 mg/dL in patients with more severe disease. Guidelines developed by the ACR and EULAR strongly recommend the use of a treat-to-target approach to reduce serum urate levels. Xanthine oxidase inhibitors, such as allopurinol and febuxostat, are the current standard of care for lowering serum urate levels in patients with gout.
Terkeltaub et al. evaluated the safety and efficacy of the novel, nonpurine xanthine oxidase inhibitor tigulixostat for lowering serum urate levels in patients with gout and hyperuricemia.
In this multicenter, double-blind, dose-finding clinical trial, the researchers randomly assigned patients with gout and hyperuricemia to receive either 50, 100 or 200 mg of oral tigulixostat daily or placebo for 12 weeks. All patients also received 0.6 mg of colchicine daily for gout flare prophylaxis. The study’s primary end point was the proportion of patients who achieved a serum urate level of <5.0 mg/dL at week 12.
A total of 143 patients were randomized to receive tigulixostat: 34 in the 50 mg-dose group, 38 in the 100 mg-dose and 37 in the 200 mg-dose group. There were 34 patients in the placebo group.
A significantly greater proportion of patients treated with tigulixostat achieved the target serum urate level of <5.0 mg/dL at week 12 than those who received placebo. The mean percentage change in serum urate levels from baseline was also significantly greater in the tigulixostat-treated groups, ranging from -38.8% to -61.8%, than in the placebo group at all time points (P<0.0001).
The percentages of patients who experienced gout flares and required rescue treatment with colchicine were comparable in the treatment and placebo groups, with 12.9%, 13.2% and 10.8% in the 50, 100 and 200 mg tigulixostat-treatment groups, respectively, and 9.4% in the placebo group. Gout flare was also the most frequently reported treatment-emergent adverse event.
During the study, the incidence of adverse events was similar across all groups, ranging 50–56.8%. Adverse events were mild or moderate in their severity.
At all three doses studied, tigulixostat significantly lowered the serum urate levels of patients with gout and hyperuricemia more than placebo. The treatment also demonstrated an acceptable safety profile.
For full study details, including source material, refer to the full article.
Excerpted and adapted from:
Terkeltaub R, Lee J, Min J, et al. Serum urate–lowering efficacy and safety of tigulixostat in gout patients with hyperuricemia: A randomized, double-blind, placebo-controlled, dose-finding trial. Arthritis Rheumatol. 2023 Jul;75(7):1275–1284.