Skip to main content
Log in

Febuxostat for the Management of Hyperuricaemia in Patients with Gout

A NICE Single Technology Appraisal

PharmacoEconomics Aims and scope Submit manuscript

Abstract

As part of the National Institute for Health and Clinical Excellence (NICE) single technology appraisal (STA) process, the manufacturer of febuxostat (Adenuric®; Ipsen, UK) was invited to submit evidence for the clinical and cost effectiveness of febuxostat for the management of hyperuricaemia in patients with gout. The School of Health and Related Research Technology Appraisal Group (ScHARR-TAG) at the University of Sheffield were commissioned to act as the independent Evidence Review Group (ERG).

This article provides details of the company’s initial submission, the ERG’s clarification questions and the ERG report submitted to NICE. The decision made by NICE is provided alongside a brief comment on additional results produced by a substantially different model, which were presented by the manufacturer after the production of the appraisal consultation document.

The ERG produced a critical review of the evidence for the clinical evidence and cost effectiveness of the technology based upon the manufacturer’s submission to NICE.

The clinical evidence was derived from two head-to-head, phase III, multiarm, randomized, double blind, controlled trials comparing the efficacy and safety of febuxostat with fixed-dose allopurinol (300/100mg/day) in patients with hyperuricaemia and gout. The ERG considered that the trials were of reasonable methodological quality and measured a clinically relevant range of outcomes. Although a simple pooled analysis of the individual patientlevel data from the two trials was undertaken, the statistical approach for combining the data was considered inappropriate by the ERG as it failed to preserve randomization and introduced bias and confounding. There was substantial uncertainty in the relationships reported by the manufacturer regarding serum uric acid levels and the incidence of gout flares and underlying patient utility. The mathematical model developed was flawed and was not corrected despite ERG comments. It focused only on patients receiving febuxostat (80mg/day titrated to 120mg/day if necessary) with fixed-dose allopurinol (300/100mg/day). Sequential treatment was not modeled, nor was titrating allopurinol to 900mg/day, which is regarded as best practice. Numerous other errors were identified, which included the uncertain price of febuxostat being sampled within the probabilistic sensitivity analyses. Supplementary exploratory modelling addressing the position of febuxostat where patients were intolerant or contraindicated to allopurinol was provided to the NICE Appraisal Committee following the release of the appraisal consultation document.

The NICE Appraisal Committee concluded that febuxostat be recommended as an option for the management of chronic hyperuricaemia in gout only for people who are intolerant to allopurinol or for whom allopurinol is contraindicated.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. National Institute for Health and Clinical Excellence. Guide to the single technology appraisal (STA) process. London: NICE, 2006 Sep [online]. Available from URL: http://www.nice.org.uk/nicemedia/pdf/STA_Process_Guide.pdf [Accessed 2010 Apr 1]

    Google Scholar 

  2. Teng GG, Nair R, Saag KG. Pathophysiology, clinical presentation and treatment of gout. Drugs 2006; 66: 1547–63

    Article  PubMed  CAS  Google Scholar 

  3. Mikuls TR, Farrar JT, Bilker WB, et al. Gout epidemiology: results from the UK General Practice Research Database, 1990–1999. Ann Rheum Dis 2005; 64: 267–72

    Article  PubMed  CAS  Google Scholar 

  4. Annemans L, Spaepen E, Gaskin M, et al. Gout in the UK and Germany: prevalence, comorbidities and management in general practice 2000–2005. Ann Rheum Dis 2008; 67 (7): 960–6

    Article  PubMed  CAS  Google Scholar 

  5. Falasca GF. Metabolic diseases: gout. Clin Dermatol 2006; 24: 498–508

    Article  PubMed  Google Scholar 

  6. Yamanaka H, Togashi R, Hakoda M, et al. Optimal range of serum urate concentrations to minimize risk of gouty attacks during anti-hyperuricemic treatment. Adv Exp Med Biol 1998; 431: 13–8

    Article  PubMed  CAS  Google Scholar 

  7. Shoji A, Yamanaka H, Kamatani N. A retrospective study of the relationship between serum urate level and recurrent attacks of gouty arthritis: evidence for reduction of recurrent gouty arthritis with antihyperuricemic therapy. Arthritis Rheum 2004; 51 (3): 321–5

    Article  PubMed  CAS  Google Scholar 

  8. Zhang W, Doherty M, Bardin T, et al. EULAR evidence based recommendations for gout: part II. Management: report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis 2006; 65: 1312–24

    Article  PubMed  CAS  Google Scholar 

  9. Jordan KM, Cameron JS, Snaith M, et al., on behalf of the British Society for Rheumatology. British Society for Rheumatology and British Health Professionals in Rheumatology guideline for the management of gout. Rheumatology (Oxford) 2007; 46: 1372–4

    Google Scholar 

  10. National Institute for Health and Clinical Excellence. Health technology appraisal: febuxostat for the management of hyperuricaemia in patients with gout. Final scope. London: NICE, 2007 Aug [online]. Available from URL: http://www.nice.org.uk/nicemedia/live/11830/36209/36209.pdf [Accessed 2010 Apr 1]

    Google Scholar 

  11. National Institute for Health and Clinical Excellence. Guide to the methods of technology appraisals. London: NICE, 2008 Jun [online]. Available from URL: http://www.nice.org.uk/media/B52/A7/TAMethodsGuideUpdatedJune2008.pdf [Accessed 2010 Apr 1]

  12. Ipsen UK. Febuxostat for the treatment of gout. Single technology appraisal submission to the National Institute for Health and Clinical Excellence. Final 15 January 2008–revised 14 May 2008. London: Ipsen, 2008 [online]. Available from URL: http://www.nice.org.uk/nicemedia/live/11830/40731/40731.pdf [Accessed 2010 Apr 1]

    Google Scholar 

  13. Stevenson M, Pandor A. Febuxostat for the management of hyperuricaemia in patients with gout. Sheffield: University of Sheffield, 2008 Mar 31 [online]. Available from URL: http://www.nice.org.uk/nicemedia/live/11830/40721/40721.pdf [Accessed 2010 Apr 1]

    Google Scholar 

  14. Becker MA, Schumacher R, Wortmann RL, et al. Febuxostat compared with allopurinol in patients with hyperuricaemia and gout. N Engl J Med 2005; 353: 2450–61

    Article  PubMed  CAS  Google Scholar 

  15. Schumacher HR, Becker MA, Wortmann RL, et al. Febuxostat vs allopurinol and placebo in subjects with hyperuricaemia and gout: the 28-week APEX study [poster]. The Annual Scientific meeting of the American College of Rheumatology; 2005 Nov 16–17; San Diego (CA)

    Google Scholar 

  16. Borstad GC, Bryant LR, Abel MP, et al. Colchicine for prophylaxis of acute flares when initiating allopurinol for chronic gouty arthritis. J Rheumatol 2004; 31: 2429–32

    PubMed  CAS  Google Scholar 

  17. National Institute for Health and Clinical Excellence. Hyperuricaemia-febuxostat: appraisal consultation document. London: NICE, 2010 Mar 30 [online]. Available from URL: http://www.nice.org.uk/guidance/index.jsp?action=article&o=40696 [Accessed 2010 Apr 1]

    Google Scholar 

  18. National Institute for Health and Clinical Excellence. Appeal hearing: febuxostat for the management of hyperuricaemia in patients with gout. London: NICE, 2008 Oct [online]. Available from URL: http://www.nice.org.uk/nicemedia/live/11830/42724/42724.pdf [Accessed 2010 Apr 1]

    Google Scholar 

  19. Stevenson M. NICE single technology appraisal of febuxostat for the treatment of hyperuricaemia. London: NICE, 2008 May 12 [online]. Available from URL: http://www.nice.org.uk/nicemedia/live/11830/40722/40722.pdf [Accessed 2010 Apr 1]

    Google Scholar 

  20. National Institute for Health and Clinical Excellence. Final appraisal determination: febuxostat for the management of hyperuricaemia in people with gout. London: NICE, 2008 Aug [online]. Available from URL: http://www.nice.org.uk/nicemedia/live/11830/41648/41648.pdf. [Accessed 2010 Apr 1]

    Google Scholar 

Download references

Acknowledgements

This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment Programme (project number 07/69/01) and will be published as part of a compendium of ERG articles in Health Technology Assessment. See the HTA programme website for further project information (http://www.hta.ac.uk). This summary of the ERG report was compiled after the AC’s review.

The authors acknowledge the clinical advice provided by Dr Kelsey Jordan and Dr Michael Snaith, who are consultant rheumatologists. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of NICE or the Department of Health.

The authors have no conflicts of interest that are directly relevant to the content of this review.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Matt Stevenson.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Stevenson, M., Pandor, A. Febuxostat for the Management of Hyperuricaemia in Patients with Gout. Pharmacoeconomics 29, 133–140 (2011). https://doi.org/10.2165/11535770-000000000-00000

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/11535770-000000000-00000

Keywords

Navigation