Skip to main content

Advertisement

SpringerLink
Log in

Intervention thresholds for denosumab in the UK using a FRAX®-based cost-effectiveness analysis

  • Original Article
  • Published:
Osteoporosis International Aims and scope Submit manuscript

Abstract

Summary

The objective was to undertake a health economic analysis of denosumab for the treatment of osteoporosis in women from the UK, using the FRAX® tool. Denosumab was cost-effective in women with a risk of major osteoporotic fracture meeting or exceeding approximately 20 % who are unable to take, comply with or tolerate generic alendronate.

Introduction

Denosumab is a novel biologic agent developed for the treatment of osteoporosis, which has been shown to reduce the risk of fractures in a phase-III trial. The objective of the present study was to undertake a health economic analysis of denosumab in women from the UK. Ten-year probabilities of a major osteoporotic fracture at which denosumab is a cost-effective alternative to no treatment, generic alendronate, risedronate and strontium ranelate were estimated.

Methods

A previously published Markov model was adapted to incorporate fracture and mortality risk assessments based on absolute fracture probability, as estimated by FRAX®. The model included treatment persistence and residual effect after discontinuation.

Results

At a willingness-to-pay (WTP) of £30,000 per quality-adjusted life year and a 10-year fracture probability equivalent to a woman with a prior fragility fracture, denosumab was cost-effective compared to no treatment from the age of 70 years. At the same WTP, denosumab was—irrespective of age—cost-effective compared to no treatment at a major osteoporotic fracture probability of approximately 20 %. Denosumab was estimated to cost-effectively replace strontium, risedronate and generic alendronate at 10-year probabilities exceeding 11, 19 and 32 %, respectively.

Conclusion

FRAX® facilitates the estimation of cost-effectiveness-based intervention thresholds applicable to patients with different combinations of clinical risk factors, which more closely matches the situation in clinical practice. Denosumab is cost-effective in patients with major osteoporotic fracture probabilities meeting or exceeding approximately 20 % who are unable to take, comply with or tolerate generic alendronate.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Kanis J (2008) Assessment of osteoporosis at the primary health-care level. Technical Report. WHO Collaborating Centre, University of Sheffield, UK

  2. Kanis JA et al (2008) FRAX™ and the assessment of fracture probability in men and women from the UK. Osteoporos Int 19(4):385–397

    Article  PubMed  CAS  Google Scholar 

  3. Kanis JA et al (2007) The use of clinical risk factors enhances the performance of BMD in the prediction of hip and osteoporotic fractures in men and women. Osteoporos Int 18(8):1033–1046

    Article  PubMed  CAS  Google Scholar 

  4. Fujiwara S et al (2008) Development and application of a Japanese model of the WHO fracture risk assessment tool (FRAX). Osteoporos Int 19(4):429–435

    Article  PubMed  CAS  Google Scholar 

  5. Association Suisse contre l‘Osteoporose (2011) Osteoporose: Recommandations 2010. Bern

  6. Neuprez A et al (2009) A FRAX model for the assessment of fracture probability in Belgium. Rev Med Liege 64(12):612–619

    PubMed  CAS  Google Scholar 

  7. Grossman JM et al (2010) American College of Rheumatology 2010 recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Care Res (Hoboken) 62:15–26

    Google Scholar 

  8. NOF (2008) Physician's guide to prevention and treatment of osteoporosis. National Osteoporosis Foundation, Washington, DC

    Google Scholar 

  9. Socialstyrelsen (2010) Nationella riktlinjer för rörelseorganens sjukdomar 2012. Osteoporos, artros, inflammatorisk ryggsjukdom och ankyloserande spondylit, psoriasisartrit och reumatoid artrit. Stöd för styrning och ledning. 1-116. Publicerad

  10. Papaioannou A et al (2010) Clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: summary. Cmaj 182(17):1864–1873

    PubMed  Google Scholar 

  11. U.S. Preventive Services Task Force (2011) Screening for osteoporosis: U.S. preventive services task force recommendation statement. Ann Intern Med 154(5):356–364

    Google Scholar 

  12. Kanis JA et al (2008) European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int 19(4):399–428

    Article  PubMed  CAS  Google Scholar 

  13. Kurth AA, Pfeilschifter J (2007) Diagnosis and treatment of postmenopausal osteoporosis and osteoporosis in men. German Guidelines Update 2006. Orthopade 36(7):683–690, quiz 691

    Article  PubMed  CAS  Google Scholar 

  14. Compston J et al (2009) Guidelines for the diagnosis and management of osteoporosis in postmenopausal women and men from the age of 50 years in the UK. Maturitas 62(2):105–108

    Article  PubMed  CAS  Google Scholar 

  15. National Osteoporosis Foundation (2008) Clinician's guide to prevention and treatment of osteoporosis. National Osteoporosis Foundation, Washington, DC

    Google Scholar 

  16. National Institute for Health and Clinical Excellence (2010) Final appraisal determination 160. Alendronate, etidronate, risedronate, raloxifene and strontium ranelate for the primary prevention of osteoporotic fragility fractures in postmenopausal women. National Institute for Health and Clinical Excellence, London

    Google Scholar 

  17. National Institute for Health and Clinical Excellence (2010) Final appraisal determination 161. Alendronate, etidronate, risedronate, raloxifene, strontium ranelate and teriparatide for the secondary prevention of osteoporotic fragility fractures in postmenopausal women. National Institute for Health and Clinical Excellence, London

    Google Scholar 

  18. National Institute for Health and Clinical Excellence (2010) Technology appraisals TA204: Osteoporotic fractures—denosumab. Accessed 5 June 2011; http://guidance.nice.org.uk/TA204

  19. Kanis J et al (2010) An evaluation of the NICE guidance for the prevention of osteoporotic fragility fractures in postmenopausal women. Arch Osteoporos. doi:10.1007/s11657-010-0045-5

  20. Kanis JA et al (2008) Case finding for the management of osteoporosis with FRAX—assessment and intervention thresholds for the UK. Osteoporos Int 19(10):1395–1408, Erratum published 2009 Osteoporos Int 20, 499–502

    Article  PubMed  CAS  Google Scholar 

  21. Borgstrom F et al (2010) The cost-effectiveness of risedronate in the UK for the management of osteoporosis using the FRAX. Osteoporos Int 21(3):495–505

    Article  PubMed  CAS  Google Scholar 

  22. Borgstrom F et al (2010) The cost-effectiveness of strontium ranelate in the UK for the management of osteoporosis. Osteoporos Int 21(2):339–349

    Article  PubMed  CAS  Google Scholar 

  23. Cummings SR et al (2009) Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 361(8):756–765

    Article  PubMed  CAS  Google Scholar 

  24. Li L et al (2010) Non-persistence to anti-osteoporosis medications in the UK using the general practice research database (GPRD) Rheumatology 49 Supplement 1 (OP54)

  25. Landfeldt E et al (2012) Adherence to treatment of primary osteoporosis and its association to fractures-the Swedish Adherence Register Analysis (SARA). Osteoporos Int 23(2):433–434

    Article  PubMed  CAS  Google Scholar 

  26. Jonsson B et al (2010) Cost-effectiveness of denosumab for the treatment of postmenopausal osteoporosis. Osteoporos Int 22(3):967–982

    Article  PubMed  Google Scholar 

  27. Strom O et al (2009) Incorporating adherence into health economic modelling of osteoporosis. Osteoporos Int 20(1):23–34

    Article  PubMed  CAS  Google Scholar 

  28. NICE (2008) Guide to the methods of technology appraisal. http://www.nice.org.uk/media/B52/A7/TAMethodsGuideUpdatedJune2008.pdf. Accessed 18 Jan 2012

  29. Strom O et al (2007) Cost-effectiveness of alendronate in the treatment of postmenopausal women in 9 European countries—an economic evaluation based on the fracture intervention trial. Osteoporos Int 18(8):1047–1061

    Article  PubMed  CAS  Google Scholar 

  30. Kanis J et al (2002) Treatment of established osteoporosis: a systematic review and cost-utility analysis. Health Technol Assess 6(29):1–146

    PubMed  CAS  Google Scholar 

  31. Stevenson M et al (2005) A systematic review and economic evaluation of alendronate, etidronate, risedronate, raloxifene and teriparatide for the prevention and treatment of postmenopausal osteoporosis. Health Technol Assess. 2005 Jun;9(22):1–160

    PubMed  CAS  Google Scholar 

  32. Strom O et al (2010) FRAX and its applications in health economics—cost-effectiveness and intervention thresholds using bazedoxifene in a Swedish setting as an example. Bone 47(2):430–437

    Article  PubMed  CAS  Google Scholar 

  33. Seeley DG et al (1991) Which fractures are associated with low appendicular bone mass in elderly women? The Study of Osteoporotic Fractures Research Group. Ann Intern Med 115(11):837–842

    PubMed  CAS  Google Scholar 

  34. National Institute for Health and Clinical Excellence (2008) Systematic reviews of clinical effectiveness prepared for the guideline osteoporosis: “assessment of fracture risk and the prevention of osteoporotic fractures in individuals at high risk”. http://www.nice.org.uk/guidance/index.jsp?action=byID&o=11621. Accessed 12 March 2011

  35. Freemantle N et al (2011) Final results of the DAPS (Denosumab Adherence Preference Satisfaction) study: a 24-month, randomized, crossover comparison with alendronate in postmenopausal women. Osteoporos Int 23(1):317–326

    Article  PubMed  Google Scholar 

  36. Stevenson M, Davis S (2006) Analyses of the cost-effectiveness of pooled alendronate and risedronate, compared with strontium ranelate, raloxifene, etidronate and teriparatide. Accessed 13 May 2008; http://www.nice.org.uk/page.aspx?o=370643

  37. Reginster JY et al (2009) Long-term treatment of postmenopausal osteoporosis with strontium ranelate: results at 8 years. Bone 45(6):1059–1064

    Article  PubMed  CAS  Google Scholar 

  38. Singer BR et al (1998) Epidemiology of fractures in 15,000 adults: the influence of age and gender. J Bone Joint Surg Br 80(2):243–248

    Article  PubMed  CAS  Google Scholar 

  39. de Lusignan S et al (2006) Using computers to identify non-compliant people at increased risk of osteoporotic fractures in general practice: a cross-sectional study. Osteoporos Int 17(12):1808–1814

    Article  PubMed  Google Scholar 

  40. Kanis JA et al (2007) Glucocorticoid-induced osteoporosis: a systematic review and cost-utility analysis. Health Technol Assess 11(7):iii–iv, ix-xi, 1–231

    PubMed  CAS  Google Scholar 

  41. National Statistics: The official UK statistics site. www.statistics.gov.uk. Accessed 14 January 2011

  42. Johnell O et al (2004) Mortality after osteoporotic fractures. Osteoporos Int 15(1):38–42

    Article  PubMed  CAS  Google Scholar 

  43. Stevenson M, Davis S, Kanis J (2006) The hospitalization costs and outpatient costs of fragility fractures. Women's Health Med 4:149–151

    Article  Google Scholar 

  44. Kanis JA et al (2001) The burden of osteoporotic fractures: a method for setting intervention thresholds. Osteoporos Int 12(5):417–427

    Article  PubMed  CAS  Google Scholar 

  45. Borgstrom F et al (2006) Costs and quality of life associated with osteoporosis-related fractures in Sweden. Osteoporos Int 17(5):637–650

    Article  PubMed  Google Scholar 

  46. Ström O et al (2008) Long-term cost and effect on quality of life of osteoporosis-related fractures in Sweden. Acta Orthop 79(2):269–280

    Article  PubMed  Google Scholar 

  47. Curtis L (2010) Unit Costs of Health and Social Care. http://www.pssru.ac.uk/pdf/uc/uc2010/uc2010.pdf. Accessed 1 Dec 2010

  48. Jonsson B et al (1996) Cost-effectiveness of fracture prevention in established osteoporosis. Scand J Rheumatol Suppl 103:30–38

    Article  PubMed  CAS  Google Scholar 

  49. Swedish National Inpatient Register and Causes of Death Register, The Swedish National Board of Health Centre - The Epidemiological Centre, http://www.sos.se/epc/epceng.htm. Accessed 1 Dec 2011

  50. Kanis JA et al (2004) Excess mortality after hospitalisation for vertebral fracture. Osteoporos Int 15(2):108–112

    Article  PubMed  Google Scholar 

  51. Bliuc D et al (2009) Mortality risk associated with low-trauma osteoporotic fracture and subsequent fracture in men and women. Jama 301(5):513–521

    Article  PubMed  CAS  Google Scholar 

  52. Kanis JA et al (2003) The components of excess mortality after hip fracture. Bone 32(5):468–473

    Article  PubMed  CAS  Google Scholar 

  53. Borgstrom F et al (2006) An economic evaluation of strontium ranelate in the treatment of osteoporosis in a Swedish setting: based on the results of the SOTI and TROPOS trials. Osteoporos Int 17(12):1781–1793

    Article  PubMed  CAS  Google Scholar 

  54. Kanis JA et al (2008) The cost-effectiveness of alendronate in the management of osteoporosis. Bone 42(1):4–15

    Article  PubMed  CAS  Google Scholar 

  55. Kind P et al (1998) Variations in population health status: results from a United Kingdom national questionnaire survey. Br Med J 316(7133):736–741

    Article  CAS  Google Scholar 

  56. Dolan P (1997) Modeling valuations for EuroQol health states. Med Care 35(11):1095–1108

    Article  PubMed  CAS  Google Scholar 

  57. Stevenson M, Davis S (2006) Analyses of the cost-effectiveness of pooled alendronate and risedronate, compared with strontium ranelate, raloxifene, etidronate and teriparatide (NICE). The University of Sheffield, School of Health and Related Research, Sheffield

    Google Scholar 

  58. Borgstrom F et al (2004) Cost effectiveness of raloxifene in the treatment of osteoporosis in Sweden: an economic evaluation based on the MORE study. PharmacoEconomics 22(17):1153–1165

    Article  PubMed  Google Scholar 

  59. Kanis JA et al (2008) Case finding for the management of osteoporosis with FRAX((R))-assessment and intervention thresholds for the UK. Osteoporos Int 19(10):1395–1408

    Article  PubMed  CAS  Google Scholar 

  60. Cummings SR et al (1998) Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. Jama 280(24):2077–2082

    Article  PubMed  CAS  Google Scholar 

  61. Scotland G et al (2011) Denosumab for the prevention of osteoporotic fractures in post-menopausal women: a NICE single technology appraisal. PharmacoEconomics 29(11):951–961

    Article  PubMed  Google Scholar 

  62. van Staa TP et al (2000) Oral corticosteroids and fracture risk: relationship to daily and cumulative doses. Rheumatology (Oxford) 39(12):1383–1389

    Article  Google Scholar 

  63. Kanis JA et al (2005) Alcohol intake as a risk factor for fracture. Osteoporos Int 16(7):737–742

    Article  PubMed  Google Scholar 

  64. Kanis JA et al (2011) Interpretation and use of FRAX in clinical practice. Osteoporos Int 22(9):2395–2411

    Article  PubMed  CAS  Google Scholar 

  65. Delmas PD et al (2003) Severity of prevalent vertebral fractures and the risk of subsequent vertebral and nonvertebral fractures: results from the MORE trial. Bone 33(4):522–532

    Article  PubMed  CAS  Google Scholar 

  66. Klotzbuecher CM et al (2000) Patients with prior fractures have an increased risk of future fractures: a summary of the literature and statistical synthesis. J Bone Miner Res 15(4):721–739

    Article  PubMed  CAS  Google Scholar 

  67. Kanis JA et al (2011) A reappraisal of generic bisphosphonates in osteoporosis. Osteoporos Int

  68. McCloskey EV et al (2009) Ten-year fracture probability identifies women who will benefit from clodronate therapy—additional results from a double-blind, placebo-controlled randomised study. Osteoporos Int 20(5):811–817

    Article  PubMed  CAS  Google Scholar 

  69. Kanis JA et al (2009) Bazedoxifene reduces vertebral and clinical fractures in postmenopausal women at high risk assessed with FRAX. Bone 44(6):1049–1054

    Article  PubMed  CAS  Google Scholar 

  70. McCloskey EV, Johansson H, Oden A, (2012) Denosumab reduces the risk of all osteoporotic fractures in postmenopausal women, particularly in those with moderate to high fracture risk as assessed with FRAX®. J Bone Miner Res. doi:10.1002/jbmr.1606

Download references

Conflicts of interest

This study was sponsored by Amgen. Amgen did not participate in the design, conduct or the writing of this paper.

Author information

Authors and Affiliations

  1. Medical Management Centre, Karolinska Institutet, Stockholm, Sweden

    O. Ström

  2. Stockholm School of Economics, Stockholm, Sweden

    B. Jönsson

  3. WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Beech Hill Road, Sheffield, S10 2RX, UK

    J. A. Kanis

Authors
  1. O. Ström
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B. Jönsson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. A. Kanis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. A. Kanis.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ström, O., Jönsson, B. & Kanis, J.A. Intervention thresholds for denosumab in the UK using a FRAX®-based cost-effectiveness analysis. Osteoporos Int 24, 1491–1502 (2013). https://doi.org/10.1007/s00198-012-2115-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-012-2115-6

Keywords

Search

Navigation