Tigulixostat may significantly lower serum urate (SUA) levels in patients with gout and hyperuricemia, according to study results published in Arthritis & Rheumatology.
The aim of the study was to determine the efficacy and safety of the nonpurine xanthine oxidase inhibitor (XOI) tigulixostat in reducing levels of SUA in patients with gout and hyperuricemia.
Researchers conducted a randomized, double-blind, placebo-controlled, dose-finding phase 2 trial (ClinicalTrials.gov Identifier: NCT03934099) with parallel groups across 42 study centers in the US.
Individuals included in the study had hyperuricemia and a gout diagnosis. After completing the washout period, participants were randomly assigned to receive 50 mg, 100 mg, or 200 mg of tigulixostat or placebo for 12 weeks. All participants also received colchicine as gout flare prophylaxis.
The primary endpoint was the percentage of participants with SUA levels below 5.0 mg/dL at week 12.
Secondary endpoints included the percentage of participants with SUA levels below 6.0 mg/dL at week 12; those with SUA levels below 5.0 mg/dL at each visit; changes in SUA levels from baseline; and the percentage of participants with gout flares.
A total of 143 individuals, aged between 18 and 75 years, received tigulixostat 50 mg (n=34), 100 mg (n=38), or 200 mg (n=37), or placebo (n=34).
A significantly greater percentage of individuals in the tigulixostat groups (47.1% at 50 mg, 44.7% at 100 mg, and 62.2% at 200 mg) vs those in the control group (2.9%; P <.0001) reached SUA levels of less than 5.0 mg/dL at week 12. Compared with participants in the control group, those in the tigulixostat groups had higher mean rates of change in SUA levels (-38.8% to -61.8%; P <.0001) from baseline.
Across all groups, 9.4% to 13.2% of participants required rescue treatment for gout flares. Adverse effects from treatment were mild to moderate and occurred at similar rates across all groups (50.0%-56.8%). Limitations of the study included the lack of use of an active comparator XOI and the relatively brief treatment period.
The study authors concluded, “… tigulixostat at all  doses significantly lowered [SUA] levels in patients with [gout and] hyperuricemia compared to placebo. Tigulixostat was generally well tolerated at all dose levels without clinically noticeable safety issues.”
However, they noted, “The efficacy and safety of tigulixostat in patients with chronic gouty arthritis warrant long-term clinical studies.”
Disclosure: This research was supported by LG Chem, Ltd. Please see the original reference for a full list of disclosures.
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 (CLUE). Arthritis Rheumatol. Published online January 17, 2023. doi:10.1002/art.42447