Phase II results support extended-release febuxostat in gout patients with renal impairment
medwireNews: Exploratory findings from a phase II trial suggest that the immediate and extended release formulations of febuxostat both have favorable efficacy and safety profiles in patients with gout and moderate renal impairment.
Febuxostat immediate release (IR) “is indicated for the management of hyperuricemia in patients with gout by lowering urate levels,” and “can be used in patients with mild-to-moderate renal impairment without the need for dose adjustments,” say Lhanoo Gunawardhana (Takeda Pharmaceuticals, Deerfield, Illinois, USA) and study co-authors in Arthritis Research & Therapy.
The extended release (XR) formulation “was developed with the aim of providing equal or greater reductions in sUA [serum uric acid] levels compared with the IR formulation, with reduced incidence of treatment-initiated flares due to an altered pattern of drug exposure,” they add.
In their trial, Gunawardhana and team randomly assigned patients with sUA levels of 8.0 mg/dL or higher and an estimated glomerular filtration rate of at least 30 but less than 60 mL/min per 1.73 m2 to receive 3 months of treatment with febuxostat XR or IR at a dose of 40 or 80 mg once daily, or to receive placebo.
At the 3-month follow-up, a significantly higher proportion of patients receiving either formulation of febuxostat compared with placebo achieved sUA levels below 5.0 mg/mL, at 13.5–44.7% versus 0.0%.
Among patients receiving the 40 mg dose of febuxostat, those given the XR formulation were significantly more likely than those given the IR formulation to meet target sUA levels, with rates of 35.9% versus 13.5%, but this difference was not observed among patients taking the 80 mg dose.
Patients treated with the XR compared with the IR formulation of febuxostat 40 mg were also more likely to achieve sUA levels below 6.0 mg/mL and less likely to experience gout flares, but the differences were not statistically significant.
These findings suggest that febuxostat 40 mg XR may have treatment benefits over the IR formulation, but superior efficacy was not seen at the 80 mg dose, say the researchers.
They report that the incidence of treatment-related adverse events was “low across all treatment groups,” with 5.8% of participants experiencing such events, and the majority were mild or moderate in severity.
The team concludes that their results “support prior reports on the safety and efficacy of febuxostat in patients with gout and moderate renal impairment, and suggest that both the XR and IR formulations of febuxostat are effective and well tolerated in patients with gout and moderately impaired renal function.”
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