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

Abstract

Objectives: To determine whether febuxostat with stepwise dose increase is as useful as colchicine prophylaxis in reducing gout flares during the initial introduction of urate-lowering therapy in patients with gout in comparison with febuxostat with no dose titration.

Methods: In this prospective, multicentre, randomised open-label comparative study, patients were randomised to group A (stepwise dose increase of febuxostat from 10 to 40 mg/day), group B (fixed-dose febuxostat 40 mg/day plus colchicine 0.5 mg/day) or group C (fixed-dose febuxostat 40 mg/day) and observed for 12 weeks. Gout flare was defined as non-steroidal anti-inflammatory drug use for gout symptoms.

Results: A total of 255 patients were randomised, and 241 patients were treated. Among the treated patients, gout flares were experienced by 20/96 (20.8%) in group A, 18/95 (18.9%) in group B and 18/50 (36.0%) in group C. The incidence of flare was significantly lower in groups A and B than that in group C (P=0.047 and P=0.024, respectively), although the differences were not significant after correction for multiple comparisons. No significant difference was noted between the incidence of gout flare in groups A and B.

Conclusions: Our data suggested that stepwise dose increase of febuxostat and low-dose colchicine prophylaxis effectively reduced gout flares in comparison with fixed-dose febuxostat alone. Stepwise dose increase of febuxostat may be an effective alternative to low-dose colchicine prophylaxis during the introduction of urate-lowering therapy.

Trial registration number: UMIN 000008414.

Keywords: arthritis; gout; treatment.

Figure 1

Patient disposition.

Figure 2

Incidence of gout flares during the randomised period. Incidence of gout flares during the first 12 weeks (randomised period) in group A (stepwise dose increase of febuxostat from 10 to 40 mg/day), group B (febuxostat 40 mg/day plus colchicine 0.5 mg/day) and group C (febuxostat 40 mg/day). The overall Pearson χ² test was not significant. See text for details. *P<0.05 vs group C.

Figure 3

Number of gout flares during the study period. Number of gout flares per patient during the first 12 weeks (randomised period) (A) and the second 12 weeks (observation period) (B). Group A (stepwise dose increase of febuxostat from 10 to 40 mg/day), group B (febuxostat 40 mg/day plus colchicine 0.5 mg/day) and group C (febuxostat 40 mg/day).

Figure 4

Percentage of patients with serum urate level ≤6.0 mg/dL (356.91 µmol/L) in the three randomised groups. Group A (stepwise dose increase of febuxostat from 10 to 40 mg/day), group B (febuxostat 40 mg/day plus colchicine 0.5 mg/day) and group C (febuxostat 40 mg/day). The number of patients for calculations based on urate data at each weekly time point in each group is shown below the figure. *P<0.001 vs group B or group C.