A URAT1 inhibitor which is undergoing clinical stage development for gout and tophaceous gout known as AR882 lowers serum urate (sUA) substantially in patients, according to data presented at the American College of Rheumatology 2023 Convergence.¹

The investigators of this proof-of-concept study, a 3-month phase 2b trial, looked at the impact of AR882 as opposed to allopurinol on the decrease of clinically visible tophi for individuals that have gout. They did this through the use of caliper measurements as well as Dual Energy Computer Tomography (DECT).

This global phase 2 research involved the recruitment of 42 individuals with gout and subcutaneous tophi, which the team randomized into 3 distinct treatment arms: once-per-day AR882 75 mg, once-per-day AR882 50 mg plus allopurinol, and once-per-day allopurinol up to 300 mg at a 1:1:1 ratio.

The investigator, led by Robert T. Keenan, MD, MPH, MBA, from Arthrosi Therapeutics, used Tophi measurements with calipers that they implemented every 4 weeks for a half a year. They conducted DECT imaging at baseline and then at half a year as well.

The research team’s primary efficacy endpoint they determined was sUA change at the 3-month mark. Their secondary endpoints they determined included the resolution of target tophus area as well as change in target tophus crystal volume from the point of baseline at month 6.

Additionally, Keenan and colleagues assessed participant safety such as vital signs as well as electrocardiograms all throughout the course of their research.

Among those in the Intent-to-Treat arm of the study, the investigators noted that baseline mean sUA levels were shown to have a range between 9.1-9.6 mg/dL over all treatment arms. The mean sUA levels were shown to be reduced to 4.5 (±1.2), 4.7 (±1.4), and 6.1 (±2.0) mg/dL for 75 mg, 50 mg + allopurinol, and allopurinol groups, respectively, at the 3-month mark.

For those in the 75 mg AR882 treatment group, the research team found that 86% and 64% of those involved reached sUA < 6 and < 5 mg/dL, respectively. But among the subjects in the 50 mg AR882 + allopurinol group, the team found 77% and 69% of patients reached sUA levels < 6 and < 5 mg/dL, respectively.

The investigators reported this contrast with the allopurinol arm, where 46% and 23% of subjects reached sUA levels < 6 and < 5 mg/dL, respectively. By the 6-month mark, the investigators reported that 29% of individuals in the AR882 75 mg arm had reported complete resolution of a minimum of 1 tophus, as opposed to to 8% for both AR882 50 mg + allopurinol and allopurinol arms.

The research team found that the AR882 75 mg arm of the study had a greater reduction in their total urate crystal volume (-30.7%, -8.3 cm3) as opposed to the combination (-31.5%, -0.9 cm3) or allopurinol (-16.8%, -1.2 cm3) from the point of baseline to 6 months on DECT.

Overall, the global study used here showed that a 6-month AR882 treatment led to both safe and effective resolution of tophus, sUA reductions, and total crystal volume dissolution in those with gout who were shown to have diverse demographic data and qualities at baseline.

References

1. ^{R. Keenan, J. Wei, L. Yeh, et al. AR882, an Efficacious and Selective URAT1 Inhibitor for Patients with Chronic Gouty Arthritis and Subcutaneous Tophi: Results from a Global, Prospective, Proof-of-Concept Trial Using Dual Energy Computed Tomography. Presented at: American College of Rheumatology Convergence 2023. San Diego, CA. November 10-15, 2023.}