Potency on lowering serum uric acid in gout patients: a pooled analysis of registrative studies comparing febuxostat vs. allopurinol

M. Cutolo, M.A. Cimmino, F. Perez-Ruiz

Department of Internal Medicine, Research Laboratory and Academic Division of Clinical Rheumatology, University of Genova, Genoa, Italy. cimmino@unige.it

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• Pharmacology

OBJECTIVE: Hyperuricemia leading to urate crystal formation in tissues represents the pathophysiological mechanism of gout. Guidelines recommend a therapeutic target of serum urate concentration (sUA) <6 mg/dL, or even lower (≤5 mg/dL) in patients with large deposits. We conducted an analysis with the aim to achieve additional insights into the urate-lowering efficacy of two xanthine oxidase inhibitors, allopurinol and febuxostat.

PATIENTS AND METHODS: This was a pooled analysis of phase III trials on allopurinol and febuxostat, including 4101 patients with gout and hyperuricemia. The efficacy outcomes were: mean reduction of sUA concentration from baseline; number of patients with target sUA levels (<6.0 mg/dL or ≤5 mgdL); time to reach target sUA levels.

RESULTS: Three registrative, phase III, randomized, multicenter, placebo-controlled/allopurinol-controlled trials assessing the efficacy of febuxostat, were included. The mean reduction of sUA concentration with any dose of febuxostat was higher (-2.92±2.87 mg/dL; -27%), with respect to placebo- (-0.62±1.84 mg/dL; -5%) and allopurinol-pooled groups (-2.41±2.20 mg/dL; -24%). Moreover, febuxostat showed a higher probability to achieve the recommended target sUA concentration than allopurinol [odds ratio: 2.43 (95% CI: 2.119-2.789) and 4.05 (95% CI: 3.41-4.82) for sUA levels <6 mg/dL and ≤5 mg/dL, respectively]. Patients on any-dose febuxostat reached target sUA faster than allopurinol-treated patients (86.04±71.47 vs. 98.76±70.88 days and 52.08±49.97 vs. 90.42±68.03 days for reaching sUA levels <6 mg/dL and ≤5 mg/dL, respectively; p <0.001 for both comparisons).

CONCLUSIONS: In patients with gout and hyperuricemia, febuxostat was significantly more effective and faster than allopurinol in obtaining the recommended target sUA levels, which were reached by a higher number of patients. Therefore, febuxostat was confirmed as an effective option for the treatment of hyperuricemia in gout.

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