A stepwise dose increase of febuxostat has been associated with a reduction in gout flares comparable with that of low-dose colchicine prophylaxis but with fewer safety concerns, according to the results of a recent prospective, multicenter, randomized, open-label, comparative study published in the Annals of the Rheumatic Diseases.
In this study, which was conducted by the Febuxostat Outcome Research Towards Urate Lowering in the Next Decade (FORTUNE) consortium, researchers randomly assigned a total of 241 patients in a 2:2:1 ratio to one of three treatment regimens: group A: stepwise dose increase of febuxostat from 10 to 40 mg/day (n=96); group B: fixed-dose febuxostat 40 mg/day plus colchicine 0.5 mg/day (n=95); or group C: fixed-dose febuxostat 40 mg/day (n=50). They observed all groups for 12 weeks.
The primary end point was the incidence of gouty arthritis during the first 12 weeks of the study. Secondary end points included the number of gout flares per patient during the first 12 weeks (randomized period), the number of gout flares per patient during the second 12 weeks (observation period), and the percentage of patients with serum urate ≤6.0 mg/dL. Gout flare was defined as nonsteroidal anti-inflammatory drug use for gout symptoms.
Gout flares were experienced by 20.8% of patients in group A, 18.9% in group B, and 36.5% in group C. The incidence of flare was significantly lower in groups A and B than group C (P =.047 and P =.024, respectively); the differences were no longer significant, however, after correction for multiple comparisons. The study investigators noted no significant difference between the incidence of gout flare in groups A and B and did not report any clinically important or serious adverse events.
The researchers concluded that a stepwise dose increase in febuxostat plus low-dose colchicine prophylaxis was effective in the reduction of gout flares compared with fixed-dose febuxostat alone. They hope that this treatment strategy will help increase patient adherence and improve long-term outcomes.
Yamanaka H, Tamaki S, Ide Y, et al. Stepwise dose increase of febuxostat is comparable with colchicine prophylaxis for the prevention of gout flares during the initial phase of urate-lowering therapy: results from FORTUNE-1, a prospective, multicentre randomised study [published online November 4, 2017]. Ann Rheum Dis. doi:10.1136/annrheumdis-2017-211574.