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

ObjectivesTo 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.MethodsIn 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.ResultsA 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.ConclusionsOur 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 numberUMIN 000008414.

Simultaneous determination of colchicine and febuxostat in rat plasma: Application in a rat pharmacokinetic study

“…The validation parameters were robust and reproducible, including the ISR, which confirmed the performance of the bioanalytical method. We believe that the simultaneous assay can be readily adopted for analysis of the two drugs in human plasma since it has been shown that a fixed dose combination of colchicine and febuxostat has therapeutic benefits in treating gout patients (Yamanaka et al, 2018).…”

“…Many strategies have been developed and are currently being used in the management of gout with the ultimate aim of optimizing the therapy, balancing the risk of side effects associated with pharmacological intervention with the established benefits the therapy provides in disease management (Ragab, Elshahaly, & Bardin, 2017; Soskind, Abazia, & Bridgeman, 2017). The recent work of Yamanaka et al (2018) has suggested the utility of a combination option of febuxostat (a xanthine oxidase inhibitor; Figure 1) and colchicine (a well‐established anti‐gout drug; Figure 1) for the effective management of gout flares. In this study involving gout patients, the data unequivocally suggested that low‐dose colchicine prophylaxis along with a step‐wise dose increase of febuxostat reduced gout flares compared with a group of patients that received a fixed dose of febuxostat as a standalone therapy (Yamanaka et al, 2018).…”

“…The recent work of Yamanaka et al (2018) has suggested the utility of a combination option of febuxostat (a xanthine oxidase inhibitor; Figure 1) and colchicine (a well‐established anti‐gout drug; Figure 1) for the effective management of gout flares. In this study involving gout patients, the data unequivocally suggested that low‐dose colchicine prophylaxis along with a step‐wise dose increase of febuxostat reduced gout flares compared with a group of patients that received a fixed dose of febuxostat as a standalone therapy (Yamanaka et al, 2018).…”

Formulation and in vitro Evaluation of Fast Dissolving Tablets of Febuxostat Using Co-Processed Excipients

“…As a non-competitive xanthine oxidase inhibitor (XOI), Febuxostat appears to be superior over the competitive XOI allopurinol, owing to its greater potency, specificity and a decreased reliance on renal excretion. It has been shown to be better than fixed-dose (300 mg) allopurinol in terms of its efficacy as a urate-lowering agent [ 8 ].…”

Fresh Perspectives on the CARES Trial and the Use of Febuxostat in an Asian Population: Comment on the Article by Choi et al

“…In particular, it is well established that febuxostat leads to a quicker drop in the level of serum urate compared with allopurinol. A recent Japanese randomized controlled trial (RCT) showed that stepwise dosing (10 mg, 20 mg, and 40 mg) of febuxostat can reduce flares from 36% to 20.8%, compared with a fixed dose of 40 mg . Therefore, it would be valid to investigate whether stepwise dosing of febuxostat starting at 10 mg or 20 mg may relieve cardiovascular (CV) side effects and flares.…”