Among gout patients, Flare Risk similar during initiation and titration of Allopurinol and Febuxostat: Study

Initiation of urate-lowering therapy in patients with gout often provokes gout flares. The degree of serum urate reduction can contribute to these attacks; the greater, the increased flare risk. Allopurinol and febuxostat represent two of the common medications used for ULT in the management of gout, and which one of these is better in reducing flare risk is uncertain.

The researchers, led by Dr. Austin Barry from the Veterans Affairs Nebraska-Western Iowa Health Care System and the University of Nebraska Medical Center, investigated whether flare risk during allopurinol initiation and titration could be compared directly with flare risk during febuxostat initiation and titration. As a background to their study, the authors performed a post-hoc analysis of the STOP-Gout trial to see which of the two agents was more efficient in reducing flare risk when such an approach was used as a treat-to-target strategy.

The STOP Gout trial was a 72-week randomized, double-blind, placebo-controlled, non-inferiority study comparing the efficacy of allopurinol and febuxostat in 940 gout patients undergoing anti-inflammatory prophylaxis. Of these, half of the participants were randomized to either of the two medication arms.

The study group assessed gout flares during the first 24 weeks of ULT, titrating the therapy with a goal serum urate less than 6 mg/dL or less than 5 mg/dL in those participants with tophi. Structured interview-based flare assessments were performed at regular intervals. Modeling of predictors of flares used multivariable Cox proportional hazards regression.

Key findings from the study include:

• One flare at a minimum was seen in 42.1% of participants receiving allopurinol and 46.2% receiving febuxostat during the first 24 weeks.

• The mean change in urate levels was similar between those subjects who did versus did not have a flare (3.24 ± 1.87 mg/dl vs 3.12 ± 1.68 mg/dl, respectively; P = 0.34).

• In multivariable analysis, no differences in flare risk were noted between febuxostat and allopurinol: aHR, 1.17; 95% CI, 0.90 to 1.53.

• There was no difference in flare risk with an increased dose of ULT compared with no increase in dose aHR 1.18, 95% CI 0.86–1.63.

• Participants with ir individuals with tophi had a 30% decreased risk of flare.

Other independent factors linked to flare risk included younger age (HR, 0.86; 95% CI, 0.78 – 0.98 per 10 years) and higher baseline serum urate levels (aHR, 1.09; 95% CI, 1.01 – 1.18 per mg/dl). The presence of stage 3 chronic kidney disease and baseline C-reactive protein levels were associated with a greater flare risk, but these did not reach statistical significance.

Allopurinol and febuxostat do not differ in terms of gout flares risk when a treat-to-target strategy is initiated and titrated with optimal anti-inflammatory prophylaxis. From these data, clinicians may use either drug to treat patients with gout with confidence, using individual patient factors to minimize flare risk.

Reference:

Barry A, Helget LN, Androsenko M, et al. A Comparison of Gout Flares with the Initiation of Treat-to-Target Allopurinol and Febuxostat: A Post-hoc Analysis of a Randomized Multicenter Trial. Arthritis Rheumatol. Published online June 24, 2024. doi:10.1002/art.42927