Prof Lisa Stamp

Serum urate concentration is a valid treatment target for reducing or eliminating gout flares supporting a treat-to-target approach for managing the condition, according to a new analysis presented at ACR Convergence 2021.

An international research team, led by rheumatologist Professor Lisa Stamp, from the University of Otago in Christchurch, analysed individual patient-level data from two randomised trials on urate-lowering therapies in people with gout carried out in the UK and in New Zealand.

From the combined data, 343 serum urate responders and 245 non-responders were identified, with response defined as a mean serum urate level below 6.0 mg/dL during the first 12 months of gout treatment.

The researchers found that significantly fewer serum urate responders had a gout flare than did serum urate non-responders between 12 and 24 months (27% versus 64%), equating to a risk reduction of 71% after adjusting for various factors including flare history and baseline serum urate.

A similar picture was seen when looking at monthly flares during the same period, with the mean number per participant significantly lower in serum urate responders than in non-responders (0.69 versus 2.09).

The researchers also found no effect of randomisation treatment allocation on the relationship between serum urate responder status and the presence or absence of gout flares, and that serum urate response was linked with tophus regression (for the combined dataset, 38 [72%] of 53 serum urate responders lost the sentinel tophus versus eight [38%] of 21 serum urate non-responders).

However, no significant differences were seen in other exploratory outcomes, such as tender and swollen joint counts, health-related quality of life and radiological outcomes.

“We have shown that achieving an average serum urate concentration of less than 6 mg/dL in a 6-month period is associated with subsequent absence of gout flares, a reduction in the number of flares, and resolution of tophi in people with gout. These findings are important in validating serum urate as a surrogate endpoint in gout,” the authors concluded in their study published simultaneously in The Lancet Rheumatology.

Study backs treat-to-target with allopurinol and febuxostat

Meanwhile, a separate study also presented at ACR Convergence found no safety or cardiovascular toxicity issues with a treat-to-target urate lowering therapy (ULT) strategy using allopurinol or febuxostat.

Dr James O’Dell, a rheumatologist at the University of Nebraska Medical Center, US, and colleagues carried out a multicentre, randomised, double-blind, non-inferiority trial comparing the safety and efficacy of the two oral therapies.

For the trial, 940 patients with gout and a serum urate concentration of 6.8 mg/dl or higher were randomised to receive either allopurinol or febuxostat between 2017 and 2019.

Patients with persistent elevated uric acid levels in the blood despite allopurinol treatment were eligible to take part in the trial, which had three phases: ULT titration from week 0-24, maintenance therapy from week 25-48 and observation with continued, stable ULT from week 49-72.

Patients received initial doses of either 100 mg of allopurinol with maximum titration to 800 mg, or 40 mg of febuxostat with maximum titration to 120 mg (reduced to 80 mg in 2019 at the request of the US Food and Drug Administration).

“Both ULTs were highly efficacious in this context with 80% of patients achieving and maintaining serum urate goals after 1 year and more than 90% achieving SU < 6.8 mg/dl,” the authors said.

There were no significant differences in efficacy between the two treatments; during the third phase, 35% of patients taking allopurinol had one or more gout flares compared to 42% of those taking febuxostat.

The research also showed that there were no differences in serious side effects between the two treatment groups, including the percentage of patients with cardiovascular events in people with or without chronic kidney disease.

“This large, randomised double-blind trial demonstrates that allopurinol, when dosed appropriately as part of a treat-to-target strategy, is non-inferior to febuxostat in the treatment of gout,” the researchers concluded.

“Moreover, the comparative efficacy and safety of these two agents extended to patients with CKD stage 3, highly relevant as nearly one in every two gout patients suffers from renal insufficiency”.