#83 Febuxostat: Precipitating Crystals of Evidence About Gout Prevention
CLINICAL QUESTION
Does febuxostat (Uloric) offer any advantages over allopurinol in preventing gout?
BOTTOM LINE
Febuxostat is not better than allopurinol for preventing gout and has a higher rate of gout flares. It should only be considered in patients who have experienced a serious adverse event with allopurinol.
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EVIDENCE
Meta-analysis1 of 5 randomized controlled trial (RCT) conducted in Canada,1 US2-4 and Japan5,6 including 4250 mostly-male patients with gout.
- 3 RCTs gave colchicine or naproxen (8 or 24 weeks2-4), whereas the other 2 trials did not provide any prophylaxis against gout flares5,6
- Febuxostat 40-240 mg compared to allopurinol 200-300 mg daily x8-52 weeks
- Gout episodes: Significant increase with febuxostat
- 43.6% versus 38.1% with allopurinol (number needed to harm [NNH]=19)
- Tophi number and size: No difference2,3
- Achieved serum uric acid <360 µmol/L: Febuxostat 66.4% versus 43.2% with allopurinol.
- 5167 and 5048 mostly-male patients, given colchicine or NSAID x8 weeks7 or NSAID for trial duration,8 randomized to febuxostat 40 or 80 mg, or allopurinol 300 mg daily for ~6 months
- No difference in gout episodes between groups
- No difference in number of tophi7
- Serum uric acid <360 µmol/L more likely with febuxostat 80 mg versus both febuxostat 40 mg and allopurinol.
- Start urate-lowering therapy at low dose and titrate up every 2-6 weeks, and use colchicine or NSAIDs for ~6 months to prevent initial flares.9-11
- Though it lowers serum uric acid, allopurinol has never been shown in RCTs to reduce gout flares.12
- Allopurinol adverse events: Mild rash, pruritus (~2%); allopurinol hypersensitivity syndrome (severe rash, fever, hepatitis and renal toxicity) [<1/1000].13,14
- Yearly costs: Febuxostat 80 mg ~$680 (approved Canadian dose), allopurinol 300 mg ~$100.15
- Febuxostat cardiovascular safety has been questioned16 and is being studied (NCT01101035).
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