Febuxostat a promising urate-lowering treatment in patients with renal impairment
Both the extended- and immediate-release formulations of febuxostat are effective and well tolerated in the treatment of gout patients with normal or impaired renal function, according to the results of a phase III trial.
“[F]ebuxostat XR [extended release] formulations were developed with the aim of providing comparable or superior urate-lowering efficacy vs their febuxostat IR [immediate release] counterparts, with reductions in treatment-initiated flares due to a more stable drug exposure profile,” the investigators said.
Based on the present data, equivalent doses of febuxostat XR and IR have similar treatment effects on serum urate (sUA) levels, showing the potential to manage hyperuricaemia in patients with renal impairment, for whom treatment options are limited, they added.
In the trial, 1,783 patients (mean age 55.1 years; 88.4 percent male) with a history of gout and normal or impaired (mild to severe) renal function were randomized to receive once-daily treatment with placebo (n=357), febuxostat IR 40 mg (n=357) or 80 mg (n=357), or XR 40 mg (n=355) or 80 mg (n=357) orally for 3 months. The overall mean serum urate (sUA) at baseline was 9.61 mg/dL, and 65.1 percent of patients had baseline sUA ≥9.0 mg/dL.
At month 3, the primary endpoint of sUA <5.0 mg/dL occurred with greater frequency across all febuxostat formulation and dose groups vs the placebo group (p<0.001 for all comparisons). The proportion of patients achieving this endpoint was greater in the XR vs IR 40-mg group (25.9 percent vs 15.7 percent; p=0.001) but did not differ significantly between the XR vs IR 80-mg group (50.1 percent vs 42.6 percent). [Arthritis Rheumatol 2018;doi:10.1002/art.40685]
Similar results were obtained for the secondary endpoint of sUA <6.0 mg/dL, with the study drug showing superiority over placebo (p<0.001 for all comparisons), whereas treatment effects were comparable between equivalent doses of XR and IR formulations (40 mg: 48.2 percent vs 40.3 percent; 80 mg: 61.1 percent vs 57.7 percent). On the other hand, the number of patients with ≥1 gout flare requiring treatment over 3 months was similar across treatment groups (range, 20.7–27.2 percent).
Of note, the superior urate-lowering effects of febuxostat vs placebo were seen across renal function subgroups, including patients with severe renal impairment.
The study drug was well tolerated. Commonly reported TEAEs—such as diarrhoea, hypertension, nasopharyngitis, arthralgia and upper respiratory tract infection—were evenly distributed across the renal function subgroups, with no apparent trends emerging between febuxostat doses or formulations.
“This trial represents the largest investigation of febuxostat in patients with renal impairment, including severe renal impairment, and the stratification of randomization by renal function (severe or not severe) helped to maintain a balanced distribution of patients with various degrees of renal impairment across treatment groups at baseline,” the investigators said.
Despite the presence of several limitations, the results add to the growing evidence supporting the use of febuxostat in the management of hyperuricaemia in patients with renal impairment, they added.