VA-sponsored trial
The study was conducted at 19 Veterans Affairs medical centers and two non-VA sites. The trial was divided into dose-titration, maintenance, and observation phases, each lasting 24 weeks.
A total of 950 participants with gout and a serum urate concentration 6.8 mg/dL or greater were randomly assigned on a 1:1 basis to receive allopurinol 100-800 mg or febuxostat 40 mg to 80/120 mg daily. In 2019, the Food and Drug Administration requested that the maximum titrated dose of febuxostat in the trial be capped at 80 mg daily. All patients stopped prophylaxis with NSAIDs, colchicine, or prednisone before the observation phase.
Patients with persistent hyperuricemia despite treatment with allopurinol were eligible, and these patients were started in the titration phase at their current dose.
The mean patient age was 62.9 years in the allopurinol arm and 61.3 years in the febuxostat arm. Men comprised 98% of patients in each study arm.
The racial/ethnic distribution of patients was similar between the groups. In all, 38.7% of patients assigned to allopurinol and 36% assigned to febuxostat had CKD stages 1-3. (Patients with stage 4 or 5 CKD were excluded from the study.)
A gout flare occurred if a participants reported three or more symptoms of tender, warm, swollen joints, or gout flare, or if the participant reported use of medication for gout flare in the observation phase during weeks 49-72.
As noted before, the trial met its primary endpoint, with 36.5% of patients on allopurinol reporting gout flare in the observation phase, compared with 43.5% on febuxostat (P for noninferiority < .001).
Among patients with CKD stage 3, the respective percentages of patients reporting at least one gout flare in the observation phase were 31.9% and 45.3% (P for noninferiority < .001).
Approximately 80% of patients in each arm had mean serum urate concentrations less than 6.0 mg/dL during the maintenance phase (weeks 36, 42, and 48).
In each arm, about 20% of patients left the study before completing 72 weeks of follow-up. Serious adverse events occurred in 26.7% of patients assigned to allopurinol and 26.1% of patients assigned to febuxostat.
Cardiovascular adverse events occurred in 8.1% and 6.8%, respectively. There were three cases of cardiovascular death in the allopurinol arm and one in the febuxostat arm. Nonfatal myocardial infarction occurred in two and four patients, respectively, stroke in one and two, and unstable angina requiring urgent revascularization in four and three patients.
In the question-and-answer session of the briefing, this news organization asked Dr. Thomas whether he would use the agents interchangeably in his practice. He replied “no, I start off with allopurinol in all of my patients, even those with chronic kidney disease, because it has been shown to be safe. I start off at a very low dose, go up slowly, [and] if they have a reaction, I change it to febuxostat.”
The study was supported by the U.S. Department of Veterans Affairs. Dr. O’Dell and Dr. Thomas have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.