The efficacy and safety of febuxostat for urate lowering in gout patients ≥65 years of age

Abstract

Background: The incidence of gout rises with increasing age. Management of elderly (≥65 years) gout patients can be challenging due to high rates of comorbidities, such as renal impairment and cardiovascular disease, and concomitant medication use. However, there is little data specifically addressing the efficacy and safety of available urate-lowering therapies (ULT) in the elderly. The objective of this post hoc analysis was to examine the efficacy and safety of ULT with febuxostat or allopurinol in a subset of elderly subjects enrolled in the CONFIRMS trial.

Methods: Hyperuricemic (serum urate [sUA] levels ≥ 8.0 mg/dL) gout subjects were enrolled in the 6-month, double-blind, randomized, comparative CONFIRMS trial and randomized, 1:1:1, to receive febuxostat, 40 mg or 80 mg, or allopurinol (200 mg or 300 mg based on renal function) once daily. Flare prophylaxis was provided throughout the study duration.Study endpoints were the percent of elderly subjects with sUA <6.0 mg/dL at the final visit, overall and by renal function status, percent change in sUA from baseline to final visit, flare rates, and rates of adverse events (AEs).

Results: Of 2,269 subjects enrolled, 374 were elderly. Febuxostat 80 mg was significantly more efficacious (82.0%) than febuxostat 40 mg (61.7%; p < 0.001) or allopurinol (47.3%; p < 0.001) for achieving the primary efficacy endpoint. Febuxostat 40 mg was also superior to allopurinol in this population (p = 0.029). In subjects with mild-to-moderate renal impairment, significantly greater ULT efficacy was observed with febuxostat 40 mg (61.6%; p = 0.028) and febuxostat 80 mg (82.5%; p < 0.001) compared to allopurinol 200/300 mg (46.9%). Compared to allopurinol 200/300 mg, the mean percent change in sUA from baseline was significantly greater for both febuxostat 80 mg (p < 0.001) and febuxostat 40 mg (p = 0.011) groups. Flare rates declined steadily in all treatment groups. Rates of AEs were low and comparable across treatments.

Conclusions: These data suggest that either dose of febuxostat is superior to commonly prescribed fixed doses of allopurinol (200/300 mg) in subjects ≥65 years of age with high rates of renal dysfunction. In addition, in this high-risk population, ULT with either drug was well tolerated.

Trial registration: clinicaltrials.gov NCT#00430248.

Trial registration: ClinicalTrials.gov NCT00430248.

Figures

Figure 1

Flow of Subjects Through the Study.

Figure 2

Achievement of sUA <6.0 mg/dL--All Subjects (Primary Endpoint) and by Renal Function. Data regarding the percentage of subjects with normal renal function with sUA <6.0 mg/dL is not presented due to the low number of subjects in this group (N = 6). ap = 0.029 vs allopurinol; bp ≤ 0.001 vs febuxostat 40 mg; cp < 0.001 vs allopurinol; dp = 0.004 vs allopurinol.

Figure 3

Mean Percent Change From Baseline In Serum Urate at Each Scheduled Visit. ap < 0.001 vs allopurinol; bp < 0.001 vs febuxostat 40 mg; cp ≤ 0.027 vs allopurinol. Error bars represent standard deviation.