Skip to main content
Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 2005 Feb 11;64(8):1174–1179. doi: 10.1136/ard.2004.032789

Cost effectiveness of etanercept (Enbrel) in combination with methotrexate in the treatment of active rheumatoid arthritis based on the TEMPO trial

G Kobelt 1, P Lindgren 1, A Singh 1, L Klareskog 1
PMCID: PMC1755590  PMID: 15708879

Abstract

Objective: To estimate the cost effectiveness of combination treatment with etanercept plus methotrexate in comparison with monotherapies in patients with active rheumatoid arthritis (RA) using a new model that incorporates both functional status and disease activity.

Methods: Effectiveness data were based on a 2 year trial in 682 patients with active RA (TEMPO). Data on resource consumption and utility related to function and disease activity were obtained from a survey of 616 patients in Sweden. A Markov model was constructed with five states according to functional status (Health Assessment Questionnaire (HAQ)) subdivided into high and low disease activity. The cost for each quality adjusted life year (QALY) gained was estimated by Monte Carlo simulation.

Results: Disease activity had a highly significant effect on utilities, independently of HAQ. For resource consumption, only HAQ was a significant predictor, with the exception of sick leave. Compared with methotrexate alone, etanercept plus methotrexate over 2 years increased total costs by €14 221 and led to a QALY gain of 0.38. When treatment was continued for 10 years, incremental costs were €42 148 for a QALY gain of 0.91. The cost per QALY gained was €37 331 and €46 494, respectively. The probability that the cost effectiveness ratio is below a threshold of €50 000/QALY is 88%.

Conclusion: Incorporating the influence of disease activity into this new model allows better assessment of the effects of anti-tumour necrosis factor treatment on patients' general wellbeing. In this analysis, the cost per QALY gained with combination treatment with etanercept plus methotrexate compared with methotrexate alone falls within the acceptable range.

Full Text

The Full Text of this article is available as a PDF (91.4 KB).

Figure 1.

Figure 1

 Uncertainty in the cost effectiveness estimates (acceptability curves) of a 2 or 10 year intervention with etanercept plus methotrexate in patients with active RA over 10 years. Acceptability curves are generated by Monte Carlo simulation, using individually drawn bootstrap estimates (1000 in this case) from the entire distribution of costs and utilities in the different Markov states. Different levels of willingness to pay for a QALY are defined and the probabilities of the cost effectiveness ratio falling below these different thresholds estimated. The probability that a 2 year treatment with etanercept plus methotrexate in a cohort of patients such as that included in the TEMPO trial is acceptable when the willingness to pay for a QALY is €50 000 is 88%. For a 10 year treatment, the probability is 71%. For a threshold value of €82 000, the probability is 99 and 98%, respectively.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Almbrand B., Johannesson M., Sjöstrand B., Malmberg K., Rydén L. Cost-effectiveness of intense insulin treatment after acute myocardial infarction in patients with diabetes mellitus; results from the DIGAMI study. Eur Heart J. 2000 May;21(9):733–739. doi: 10.1053/euhj.1999.1859. [DOI] [PubMed] [Google Scholar]
  2. Chehata J. C., Hassell A. B., Clarke S. A., Mattey D. L., Jones M. A., Jones P. W., Dawes P. T. Mortality in rheumatoid arthritis: relationship to single and composite measures of disease activity. Rheumatology (Oxford) 2001 Apr;40(4):447–452. doi: 10.1093/rheumatology/40.4.447. [DOI] [PubMed] [Google Scholar]
  3. Fenwick E., Claxton K., Sculpher M. Representing uncertainty: the role of cost-effectiveness acceptability curves. Health Econ. 2001 Dec;10(8):779–787. doi: 10.1002/hec.635. [DOI] [PubMed] [Google Scholar]
  4. Fries J. F., Spitz P., Kraines R. G., Holman H. R. Measurement of patient outcome in arthritis. Arthritis Rheum. 1980 Feb;23(2):137–145. doi: 10.1002/art.1780230202. [DOI] [PubMed] [Google Scholar]
  5. Jacobsson L., Lindroth Y., Marsal L., Tejler L. Malmömodellen för privat och offentlig reumatologisk öppenvård. Samarbete möjliggör snabbt insatt sjukdomsmodifierande behandling. Lakartidningen. 2001 Oct 24;98(43):4710–4716. [PubMed] [Google Scholar]
  6. Klareskog Lars, van der Heijde Désirée, de Jager Julien P., Gough Andrew, Kalden Joachim, Malaise Michel, Martín Mola Emilio, Pavelka Karel, Sany Jacques, Settas Lucas. Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet. 2004 Feb 28;363(9410):675–681. doi: 10.1016/S0140-6736(04)15640-7. [DOI] [PubMed] [Google Scholar]
  7. Kobelt G., Eberhardt K., Geborek P. TNF inhibitors in the treatment of rheumatoid arthritis in clinical practice: costs and outcomes in a follow up study of patients with RA treated with etanercept or infliximab in southern Sweden. Ann Rheum Dis. 2004 Jan;63(1):4–10. doi: 10.1136/ard.2003.010629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kobelt G., Eberhardt K., Jönsson L., Jönsson B. Economic consequences of the progression of rheumatoid arthritis in Sweden. Arthritis Rheum. 1999 Feb;42(2):347–356. doi: 10.1002/1529-0131(199902)42:2<347::AID-ANR18>3.0.CO;2-P. [DOI] [PubMed] [Google Scholar]
  9. Kobelt G., Jönsson L., Young A., Eberhardt K. The cost-effectiveness of infliximab (Remicade) in the treatment of rheumatoid arthritis in Sweden and the United Kingdom based on the ATTRACT study. Rheumatology (Oxford) 2003 Feb;42(2):326–335. doi: 10.1093/rheumatology/keg107. [DOI] [PubMed] [Google Scholar]
  10. Kobelt Gisela, Jönsson Linus, Lindgren Peter, Young Adam, Eberhardt Kerstin. Modeling the progression of rheumatoid arthritis: a two-country model to estimate costs and consequences of rheumatoid arthritis. Arthritis Rheum. 2002 Sep;46(9):2310–2319. doi: 10.1002/art.10471. [DOI] [PubMed] [Google Scholar]
  11. Kroot E. J., van Leeuwen M. A., van Rijswijk M. H., Prevoo M. L., Van 't Hof M. A., van De Putte L. B., van Riel P. L. No increased mortality in patients with rheumatoid arthritis: up to 10 years of follow up from disease onset. Ann Rheum Dis. 2000 Dec;59(12):954–958. doi: 10.1136/ard.59.12.954. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kvien Tore K. Epidemiology and burden of illness of rheumatoid arthritis. Pharmacoeconomics. 2004;22(2 Suppl 1):1–12. doi: 10.2165/00019053-200422001-00002. [DOI] [PubMed] [Google Scholar]
  13. Lindqvist E., Eberhardt K. Mortality in rheumatoid arthritis patients with disease onset in the 1980s. Ann Rheum Dis. 1999 Jan;58(1):11–14. doi: 10.1136/ard.58.1.11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Löthgren M., Zethraeus N. Definition, interpretation and calculation of cost-effectiveness acceptability curves. Health Econ. 2000 Oct;9(7):623–630. doi: 10.1002/1099-1050(200010)9:7<623::aid-hec539>3.0.co;2-v. [DOI] [PubMed] [Google Scholar]
  15. Pincus T., Sokka T., Wolfe F. Premature mortality in patients with rheumatoid arthritis: evolving concepts. Arthritis Rheum. 2001 Jun;44(6):1234–1236. doi: 10.1002/1529-0131(200106)44:6<1234::AID-ART213>3.0.CO;2-R. [DOI] [PubMed] [Google Scholar]
  16. Riise T., Jacobsen B. K., Gran J. T., Haga H. J., Arnesen E. Total mortality is increased in rheumatoid arthritis. A 17-year prospective study. Clin Rheumatol. 2001;20(2):123–127. doi: 10.1007/pl00011191. [DOI] [PubMed] [Google Scholar]
  17. Scott D. L., Pugner K., Kaarela K., Doyle D. V., Woolf A., Holmes J., Hieke K. The links between joint damage and disability in rheumatoid arthritis. Rheumatology (Oxford) 2000 Feb;39(2):122–132. doi: 10.1093/rheumatology/39.2.122. [DOI] [PubMed] [Google Scholar]
  18. Sonnenberg F. A., Beck J. R. Markov models in medical decision making: a practical guide. Med Decis Making. 1993 Oct-Dec;13(4):322–338. doi: 10.1177/0272989X9301300409. [DOI] [PubMed] [Google Scholar]
  19. Symmons D. P., Jones M. A., Scott D. L., Prior P. Longterm mortality outcome in patients with rheumatoid arthritis: early presenters continue to do well. J Rheumatol. 1998 Jun;25(6):1072–1077. [PubMed] [Google Scholar]
  20. Torrance G. W. Measurement of health state utilities for economic appraisal. J Health Econ. 1986 Mar;5(1):1–30. doi: 10.1016/0167-6296(86)90020-2. [DOI] [PubMed] [Google Scholar]
  21. Wallberg-Jonsson S., Ohman M. L., Dahlqvist S. R. Cardiovascular morbidity and mortality in patients with seropositive rheumatoid arthritis in Northern Sweden. J Rheumatol. 1997 Mar;24(3):445–451. [PubMed] [Google Scholar]
  22. Wolfe F., Mitchell D. M., Sibley J. T., Fries J. F., Bloch D. A., Williams C. A., Spitz P. W., Haga M., Kleinheksel S. M., Cathey M. A. The mortality of rheumatoid arthritis. Arthritis Rheum. 1994 Apr;37(4):481–494. doi: 10.1002/art.1780370408. [DOI] [PubMed] [Google Scholar]
  23. Yelin Edward, Trupin Laura, Wong Belinda, Rush Stephanie. The impact of functional status and change in functional status on mortality over 18 years among persons with rheumatoid arthritis. J Rheumatol. 2002 Sep;29(9):1851–1857. [PubMed] [Google Scholar]

Articles from Annals of the Rheumatic Diseases are provided here courtesy of BMJ Publishing Group

RESOURCES