Initiation of Febuxostat Does Not Prolong Acute Gout Flares

Febuxostat started at the onset of an acute gout flare does not prolong the duration of the current flare, according to the results of a study published in Rheumatology.1 Further, the “treat-to-target” rate was higher at the 7-day mark for the febuxostat group and the rate of recurrent flares did not increase.

While urate-lowering treatment (ULT) is important for patients with gout, there have been conflicting recommendations on starting ULT treatment during an acute flare. Typically, it is held off until the flare has resolved in order to avoid prolongation of symptoms. However, investigators theorized that starting ULT at the beginning of a flare may reduce outpatient treatment visits while increasing patient compliance.

The placebo-controlled, single-blinded, multicenter trial focused on 140 patients who were experiencing an acute gout flare that had begun within the last 72 hours. The research team sought to measure “days to resolution” of the flare, and randomized participants 1:1 to either febuxostat (40 mg/day) or placebo. Exclusion criteria included taking anti-inflammatory drugs and having taken ULT drugs in the last 6 months. The mean age of participants in the placebo group was 41.41 years and 42.13 in the febuxostat group, with a mean disease duration of 3.46 and 3.77 years, respectively.

Trial participants received diclofenac (150 mg/day) for the first 7 days and then open-labelled day 8 through 28. Patients in remission received 40 mg of febuxostat and 75 mg of diclofenac daily from day 8 through 28.

Participants assessed joint pain, swelling, tenderness, and erythema using 5- and 3-point Likert scales throughout the trial either in person at or via a video call. At baseline, pain scores for the placebo and febuxostat groups were 2.87 and 2.89, respectively, with no significant differences in the first 5 days. On day 7, a self-assessment of pain was reduced to 0.13 and 0.26. Joint swelling scores for the placebo group were 1.99 and 1.93 in the febuxostat group, which decreased to 0.13 and 0.20 on day 7. Joint tenderness scores went from 1.61 for the placebo group and 1.60 in the febuxostat group down to 0.14 and 0.19. Lastly, joint erythema scores were 1.46 and 1.40 at baseline, which decreased to 0.10 and 0.15.

Investigators also tested c-reactive proteins (CRP) via a blood analysis at baseline and at 7 days. Average CRP levels were 17.16 mg/l for the placebo group and 22.30 mg/l for the febuxostat group (P = 0.225). On day 7, CRP levels were reduced to 7.59 and 9.40 mg/L (P = 0.513). Serum uric acid (sUA) levels were tested and were significantly lower at day 7 for patients in the febuxostat group, which was to be expected.

Using an intent-to-treat (ITT) analysis, the mean days to resolution was 5.98 days in the placebo group and 6.50 days for patients taking febuxostat. In the per-protocol analysis, patients receiving the placebo had an average of 6.16 days to resolution, while the febuxostat group’s flare resolved in 6.58 days. Within 7 days, 84.38% of the placebo group had recovered from their flare, as opposed to 76.92% of patients in the febuxostat group. Recurrent gout flares were 10% for the placebo group and 6.56% for the febuxostat group during the remission period.

The study was limited by being conducted at 3 separate centers, as the consistency of diagnosis could not be guaranteed. Additionally, since the placebo was not identical in appearance to the febuxostat, investigators theorized that there may have been some observational bias from participants who noticed the difference.

“We found that initiation of febuxostat administration during an acute gout flare did not prolong acute flares, and the rate of ‘treat to target’ was higher in the febuxostat group,” investigators concluded. “This may increase patient compliance.”

Reference:

Jia E, Zhang Y, Ma W, et al. Initiation of febuxostat for acute gout flare does not prolong the current episode: a randomized clinical trial [published online ahead of print, 2021 Jan 6]. Rheumatology (Oxford). 2021;keaa908. doi:10.1093/rheumatology/keaa908