Comparing Febuxostat to Allopurinol in the Treatment of Gout

Research shows febuxostat is more effective than allopurinol in reducing serum urate levels in patients with gout.

According to the authors of “Comparative effectiveness of urate lowering with febuxostat versus allopurinol in gout: analyses from large U.S. managed care cohort,” published in Arthritis Research & Therapy, “optimal treatment of gout is based on two principles: adequate chronic use of urate-lowering therapies and aiming to achieve target serum urate (sUA) levels and anti-inflammatory therapies for acute flares and anti-inflammatory prophylaxis.” Until the approval of febuxostat (a non-purine xanthine oxidase inhibitor) in 2009, only the purine xanthine oxidase (XO) inhibitor allopurinol was available in the US for treating gout. The authors undertook a retrospective study of patterns of use of allopurinol and febuxostat in a large managed care organization to “study the change in sUA with allopurinol versus febuxostat treatment by assessing the proportion of patients achieving a post-index sUA goal of <6.0 mg/dL in the follow-up period, a clinically meaningful and important outcome for patients with gout.”

As secondary goal of the study was compare to serum creatinine (SCr) levels between allopurinol and febuxostat users.

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The authors analyzed data from patients with a prescription for either febuxostat or allopurinol for the treatment of gout over roughly a 3-year period. They looked at medical data, pharmacy data, enrollment information and laboratory results drawn from Medicare and commercial insurance claims data.

For the purposes of the study, the researchers defined the date of a patient’s first febuxostat or allopurinol filled prescription as the index date. The index date for patients who filled prescriptions for both medications was the date of the first filled prescription for febuxostat.

Patients were assigned to one of two cohorts based on their index medication. Patients treated initially with allopurinol who then switched to febuxostat were assigned to the febuxostat cohort. The authors noted that patients treated with allopurinol were permitted an index medication dose of 100‑1,500 mg/day, “because allopurinol is available in various tablet strengths.” Febuxostat-treated patients were permitted an index medication dose of 40 mg or 80 mg (the only 2 available doses). Less than 0.5% of subjects in the allopurinol cohort had a daily dose greater than 800 mg/day. The most common doses were 300 mg/day or lower dose for allopurinol and 40 mg/day for febuxostat.

Out of a final sample of 16,040 patients, 2,015 were assigned to the febuxostat cohort and 14,025 were assigned to the allopurinol cohort.

Analysis of the data showed that a higher proportion of febuxostat users compared with allopurinol users attained the sUA goal of <6.0 mg/dL (58.5% vs. 47.1%, P <.001) and the sUA goal <5.0 mg/dL (36.2% vs. 21.8%, P <.001)

Patients treated with febuxostat users also achieved target sUA goals faster than patients who received allopurinol (goal of <6.0 mg/dL: 348 days vs. 410 days, P <.001; goal of <5.0 mg/dL: 443 days vs. 501 days, P <.001).

In their discussion of these results, the authors wrote “we found that in most commonly used doses, a significantly higher proportion of patients receiving febuxostat (most common dose, 40 mg/day) achieved a target sUA of <6.0 mg/dl and <5.0 mg/dl compared to those receiving allopurinol (most common dose, 300 mg/day or lower).” A comparative study such as this can help patients, clinicians, and policy makers make better, more informed treatment decisions.

Another interesting facet of this study was that very few patients with gout received guideline-recommended care. The authors noted that “less than one-third of patients had a dose change in allopurinol and less than one-fifth in febuxostat doses after the index prescription, indicating that the dose titration as recommended by the guidelines to achieve target sUA is not a common practice.”

Also, because so many patients in the study (95%) were found to be receiving allopurinol doses of 300 mg/day or less, the authors surmised that it is likely that this dose, though commonly used in real-life practice, is subtherapeutic, and that there is “an emerging trend to increase allopurinol dose to 800 to 1,500 mg/day until target sUA is achieved.”

In all, the authors concluded that “these are important findings and indicate that febuxostat is an effective option for treatment of hyperuricemia in patients with gout,” as it was more effective and faster at achieving target sUA levels than allopurinol.