Tools for Practice


#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. 
2 RCTs conducted in China7,8 
  • 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.  
Studies’ methodological weaknesses: Selective reporting of clinical outcomes, emphasizing surrogate outcomes, and under-dosing allopurinol.  Context:  
  • 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). 
updated aug 6 2016 by ricky
February 19, 2013

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Author(s):

  • Michael R Kolber BSc MD CCFP MSc
  • Tony Nickonchuk BScPharm CDE APA

1. Faruque LI, Ehteshami-Afshar A, Wiebe N, Tjosvold L, Homik J, Tonelli M. Semin Arthritis Rheum 2013;43:367-75.

2. Becker MA, Schumacher Jr HR, Wortmann RL, et al. N Engl J Med 2005;353:2450-61.

3. Schumacher Jr HR, Becker MA, Wortmann RL, et al. Arthritis Rheum 2008;59:1540–8.

4. Becker MA, Schumacher Jr HR, Espinoza LR, et al. Arthritis Res Ther 2010;2:R63.

5. Kamatani N, Fujimori S, Hada T, et al. J Clin Rheumatol 2011;17:S44-S49.

6. Kamatani N, Fujimori S, Hada T, et al. J Clin Rheumatol 2011;17:S13-S18.

7. Huang X, Du H, Gu J, et al. Int J Rheum Dis 2014;17:679-86.

8. Xu S, Liu X, Ming J, et al. Int J Rheum Dis 2015;18:669-78.

9. Shmerling RH. JAMA 2012;308:2133-41.

10. Neogi T. Ann Intern Med 2016;165:ITC1-ITC16.

11. Borstad GC, Bryant LR, Abel MP. J Rheumatol 2004;31:2429–32.

12. Seth R, Kydd ASR, Buchbinder R, Bombardier C, Edwards CJ. Cochrane Database Syst Rev 2014;10:CD006077.

13. Chao J, Terkeltaub R. Curr Rheumatol Rep 2009;11:135-40.

14. Dalbeth N, Stamp L. Semin Dial 2007;20:391–5.

15. http://www.acfp.ca/wp-content/uploads/2014/02/ACFPPricingDoc2015-final.pdf [Accessed 3 Aug 2016]

16. Schumacher Jr HR, Becker MA, Lloyd E, et al. Rheumatology 2009;48:188–94.

Authors do not have any conflicts of interest to declare.