Skip to main content
SpringerLink
Log in

Cost Effectiveness of Tumour Necrosis Factor-α Inhibitors as First-Line Agents in Rheumatoid Arthritis

  • Original Research Article
  • Published:
PharmacoEconomics Aims and scope Submit manuscript

Abstract

Background and objective

Rheumatoid arthritis (RA) is an autoimmune disease with an unknown aetiology that results in >9 million physician visits and >250 000 hospitalisations per year in the US. Tumour necrosis factor-a (TNFa) inhibitors are effective agents in treating RA; however, their cost effectiveness as first-line agents has not been investigated. This study aimed to examine the cost effectiveness of using TNFa inhibitors (both as monotherapy and in combination with methotrexate) as first-line agents versus methotrexate (monotherapy) from a payer perspective.

Methods

A Markov model was developed utilising a discount rate of 3% per annum, a cycle length of 1 year and a lifetime time-horizon for a hypothetical cohort of US females aged 55–60 years who had been diagnosed with RA. The source of data for predicted probabilities, expected mortality rates and treatment costs in year 2005 US dollars (drug, toxicity, monitoring and hospitalisation) was from the literature. These costs are assigned in 5-year cycles (calculated from initial 1-year estimates) along with the effect on quality-adjusted life-years (QALYs), which were calculated using the Health Assessment Questionnaire score. Univariate sensitivity analyses were conducted on all relevant parameters. Results: Adalimumab, etanercept, adalimumab plus methotrexate and infliximab plus methotrexate had incremental cost-effectiveness ratios (ICERs) versus methotrexate monotherapy of $US63 769, $US89 772, $US194 589 and $US409 523 per QALY, respectively. When taking into consideration age at diagnosis, the ICER for etanercept ranged from $US84 129 to $US96 225 per QALY. In considering males for the base-case age at diagnosis, the ICER for etanercept versus methotrexate was $US85 100 per QALY. The average lifetime cost across all treatment arms in a woman diagnosed between 55 and 60 years of age was $US211 702.

Conclusion

While these ICERs cannot be used to directly compare one biological agent with another since there are no comparative trials, they do provide a valid comparison versus methotrexate as first-line agents. Depending where the cost-effectiveness threshold is drawn (i.e. whether it is considered to be $US50 000 or $US100 000 per QALY), etanercept and adalimumab may be considered relatively cost-effective first-line treatments for RA compared with methotrexate monotherapy.

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

Table I
Fig. 1
Table II
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. American College of Rheumatology. Guidelines for the management of rheumatoid arthritis: 2002 update. Arthritis Rheum 2002; 46 (2): 328–346

    Article  Google Scholar 

  2. Hochberg M. Adult and juvenile rheumatoid arthritis: current epidemiologic concepts. Epidemiol Rev 1981; 3: 27–44

    PubMed  CAS  Google Scholar 

  3. Cooper N. Economic burden of rheumatoid arthritis: a systematic review. Rheumatology 2000; 39: 28–33

    Article  PubMed  CAS  Google Scholar 

  4. Jobanputra P, Barton P, Bryan S, et al. The clinical effectiveness and cost-effectiveness of new drug treatments for rheumatoid arthritis: etanercept and infliximab. 2001 Sep 3 [online]. Available from URL: http://www.nice.org.uk/page.aspx?o=29675 [Accessed 2006 Sep 6]

    Google Scholar 

  5. Arnett F, Edworthy S, Bloch D. The American Rheumatology Association 1987 revised criteria for classification or rheumatoid arthritis. Arthritis Rheum 1988 Mar; 31 (3): 315–324

    Article  PubMed  CAS  Google Scholar 

  6. MacGregor A, Schneider H, Rigby A, et al. Characterizing the quantitative genetic contribution to rheumatoid arthritis using data from twins. Arthritis Rheum 2000; 43: 30–37

    Article  PubMed  CAS  Google Scholar 

  7. Barton A, John S, Ollier W, et al. Association between rheumatoid arthritis and polymorphisms of tumor necrosis factor II, but not tumor necrosis factor in Caucasians. Arthritis Rheum 2001; 44: 61–65

    Article  PubMed  CAS  Google Scholar 

  8. Silman A. Epidemiology and rheumatic diseases. In: Maddison P, Isenburg D, Woo P, et al., editors. Oxford textbook of rheumatology. Oxford: Oxford University Press, 1998: 811–828

    Google Scholar 

  9. Maini R, Feldman M. Immunopathogenesis of rheumatoid arthritis. In: Maddison P, Isenburg D, Woo P, Glass D, editors. Oxford textbook of rheumatology. Oxford: Oxford University Press, 1998: 983–1004

    Google Scholar 

  10. Boyce E. Rheumatoid arthritis. In: Herfindal E, Gourley D, editors. Textbook of therapeutics: drug and disease management. 7th ed. Philadelphia (PA): Lippincott Williams & Wilkins, 2000: 641–666

    Google Scholar 

  11. Lotz M. Cytokines and their receptors. In: Koopman W, editor. Arthritis and allied conditions: a textbook of rheumatology. Philadelphia (PA): Lippincott Williams & Wilkins, 1996: 439–478

    Google Scholar 

  12. Van der Heide A, Jacobs J, Bijlsma W, et al. The effectiveness of early treatment with “second-line” anti-rheumatic drugs. Ann Intern Med 1996; 124: 699–707

    PubMed  Google Scholar 

  13. Piascik P. New antibody approved for the treatment of rheumatoid arthritis. J Am Pharm Assoc 2003; 43 (2): 327–328

    Article  Google Scholar 

  14. Breedveld FC, Weisman MH, Kavanaugh AF, et al. The efficacy and safety of adalimumab (Humira®) plus methotrexate vs adalimumab alone or methotrexate alone in the early treatment of rheumatoid arthritis (RA): 1- and 2-year results of the PREMIER study [OP0013]. The Annual European Congress of Rheumatology; 2005 Jun 8–11; Vienna

    Google Scholar 

  15. St Clair W, van der Heijde D, Smolen J, et al. Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial. Arthritis Rheum 2004; 50 (11): 3432–3443

    Article  Google Scholar 

  16. Genovese MC. Etanercept vs MTX in patients with early RA. Arthritis Rheum 2002; 46 (8): 1443–1450

    Article  PubMed  CAS  Google Scholar 

  17. Cohen M, Keystone E, Weaver A. The role of biologics in optimizing RA treatment: a return to monotherapy? Rheumatology CME symposium; 2001 Nov 11–15; San Francisco (CA)

    Google Scholar 

  18. First DataBank’s national drug data file plus (NDDF Plus) [electronic database]. San Bruno (CA): First DataBank, 2005 Oct

  19. Express scripts drug trend 2002 report. Maryland Heights (MO): Express Scripts, Inc., 2003 Jun

  20. Physicians’s fee and coding guide. 16th ed. Duluth (GA): MAG Mutual Healthcare Solutions Inc., 2005

  21. Jobanputra P, Barton P. The effectiveness of infliximab and etanercept for the treatment of rheumatoid arthritis: a systematic review and economic evaluation. Health Technol Assess 2002; 6 (21): 1–99

    PubMed  CAS  Google Scholar 

  22. Healthcare Cost and Utilization Project (HCUP). 2003 inpatient data. Rockville (MD): Agency for Healthcare Research and Quality, 2003

    Google Scholar 

  23. Wolfe F, Michaud K. Lymphoma in rheumatoid arthritis: the effect of methotrexate and anti-tumor necrosis factor therapy in 18,572 patients. Arthritis Rheum 2004; 50 (6): 1740–1751

    Article  PubMed  CAS  Google Scholar 

  24. Michaud K, Messer J, Choi HK, et al. Direct medical costs and their predictors in patients with rheumatoid arthritis: a threeyear study of 7527 patients. Arthritis Rheum 2003; 48 (10): 2750–2762

    Article  PubMed  Google Scholar 

  25. Yelin E, Wanke L. An assessment of annual and long-term direct costs of RA. Arthritis Rheum 1999; 42: 1209–1218

    Article  PubMed  CAS  Google Scholar 

  26. Gold M, Russel L, Siegel J, et al. Cost-effectiveness in health and medicine. New York: Oxford Press, 1996

    Google Scholar 

  27. Kobelt G. Modeling the progression of rheumatoid arthritis: a two-country model to estimate costs and consequences of rheumatoid arthritis. Arthritis Rheum 2002; 46 (9): 2310–2319

    Article  PubMed  Google Scholar 

  28. Kobelt G, Eberhardt K, Jonsson L, et al. Economic consequences of the progression of rheumatoid arthritis in Sweden. Arthritis Rheum 1999; 42 (2): 347–356

    Article  PubMed  CAS  Google Scholar 

  29. Kobelt G, Jonsson L, Young A, et al. The cost-effectiveness of infliximab (Remicade) in the treatment of rheumatoid arthritis in Sweden and the United Kingdom based on the attract study. Rheumatology 2003; 42: 326–335

    Article  PubMed  CAS  Google Scholar 

  30. Clark W, Jobanputra P, Barton P, et al. The clinical and cost-effectiveness of anakinra for the treatment of rheumatoid arthritis in adults. 2003 Jan [online]. Available from URL: http://www.nice.org.uk/page.aspx?o=65574 [Accessed 2006 Sep 6?

    Google Scholar 

  31. Breedveld FC, Weismann MH, Kavanaugh AF, et al. A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis Rheum 2006; 54 (1): 26–37

    Article  PubMed  CAS  Google Scholar 

  32. Hay J. Evaluation and review of pharmacoeconomic models. Expert Opin Pharmacother 2004; 5 (9): 1867–1880

    Article  PubMed  Google Scholar 

  33. Keystone E, Kavanaugh A, Sharp J, et al. Radiographic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a randomized, placebo-controlled, 52-week trial. Arthritis Rheum 2004; 50 (5): 1400–1411

    Article  PubMed  CAS  Google Scholar 

  34. Klareskog L, Heijde DVD, Jager JPD, et al. 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; 363: 675–681

    Article  PubMed  CAS  Google Scholar 

  35. Lipsky PE, van der Heijde D, St Clair EW, et al. Infliximab and methotrexate in the treatment of rheumatoid arthritis. N Engl J Med 2000; 343: 1594–1602

    Article  PubMed  CAS  Google Scholar 

  36. van de Putte LBA, Atkins C, Malaise M, et al. Efficacy and safety of adalimumab as monotherapy in patients with rheumatoid arthritis for whom previous disease modifying antirheumatic drug treatment has failed. Ann Rheum Dis 2005; 63: 508–516

    Article  Google Scholar 

  37. Weinblatt M. Adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody, for the treatment of RA in patients taking concomitant MTX. Arthritis Rheum 2003; 48 (1): 35–45

    Article  PubMed  CAS  Google Scholar 

  38. Felson D, Anderson J, Meenen R. Use of short-term efficacy/toxicity tradeoffs to select second-line drugs in rheumatoid arthritis: a meta-analysis of published clinical trials. Arthritis Rheum 1992; 35: 1117–1125

    Article  PubMed  CAS  Google Scholar 

  39. Wolfe F. The mortality of rheumatoid arthritis. Arthritis Rheum 1994; 37 (4): 481–494

    Article  PubMed  CAS  Google Scholar 

  40. Young A, Dixey J, Kulinskaya E, et al. Which patients stop working because of rheumatoid arthritis? Results of five years’ follow up in 732 patients from the Early RA Study (ERAS). Ann Rheum Dis 2002; 61: 335–340

    Article  PubMed  CAS  Google Scholar 

  41. Employment and earnings report, January 2005. Washington, DC: Bureau of Labor Statistics, 2005 Sep 21 [online]. Available from URL: http://www.bls.gov/ncs/ect/home.htm [Accessed 2006 Sep 6]

  42. Yelin E, Trupin L, Katz P, et al. Association between etanercept use and employment outcomes among patients with rheumatoid arthritis. Arthritis Rheum 2003; 48 (11): 3046–3054

    Article  PubMed  Google Scholar 

  43. Brennan A, Bansback N, Reynolds A, et al. Modelling the cost-effectiveness of etanercept in adults with rheumatoid arthritis in the UK. Rheumatology 2004; 42: 62–72

    Article  Google Scholar 

  44. Bansback NJ, Regier DA, Ara R, et al. An overview of economic evaluations for drugs used in rheumatoid arthritis. Drugs 2005; 65 (4): 473–496

    Article  PubMed  Google Scholar 

  45. Viller F, Guillemin F. Compliance to drug treatment of patients with rheumatoid arthritis: a 3-year longitudinal study. J Rheumatol 1999; 26: 2114–2122

    PubMed  CAS  Google Scholar 

  46. Ollendorf DA, Massarotti E, Birbara C, et al. Frequency, predictors, and economic impact of upward dose adjustment of infliximab in managed care patients with rheumatoid arthritis. J Manag Care Pharm 2005; 11 (5): 383–393

    PubMed  Google Scholar 

  47. Wolfe F, Michaud K, Anderson J, et al. Tuberculosis infection in patients with rheumatoid arthritis and the effect of infliximab therapy. Arthritis Rheum 2004; 50 (2): 372–379

    Article  PubMed  CAS  Google Scholar 

  48. Gabriel S, Crowson C, Luthra H, et al. Modeling the lifetime costs of rheumatoid arthritis. J Rheumatol 1999; 26: 1269–1274

    PubMed  CAS  Google Scholar 

  49. Wolfe F, Zwillich S. Long-term outcomes of rheumatoid arthritis: a 23-year prospective, longitudinal study of total joint replacement and its predictors in 1600 patients with rheumatoid arthritis. Arthritis Rheum 1998; 41 (6): 1072–1082

    Article  PubMed  CAS  Google Scholar 

  50. van Vollenhoven R. Switching between biological agents. Clin Exp Rheumatol 2004; 22 Suppl. 35: S115–S121

    PubMed  Google Scholar 

  51. Wong J, Singh G, Kavanaugh A. Estimating the cost-effectiveness of 54 weeks of infliximab for rheumatoid arthritis. Am J Med 2002; 113 (5): 400–408

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This study was conducted while Dr Spalding was a graduate student at the University of Southern California, Los Angeles. Funding for this study was provided solely by the University of Southern California. Both authors made significant contributions to the intellectual content of the manuscript. Dr Hay has previously consulted with Abbott Laboratories and Dr Spalding has previously worked for a company that awarded Abbott stock as part of its stock option package.

Author information

Authors and Affiliations

  1. Astellas Pharma US, Deerfield, Illinois, USA

    James R. Spalding

  2. Department of Pharmaceutical Economics and Policy, School of Pharmacy, University of Southern California, 1540 East Alcazar Street, CHP 140, Los Angeles, California, 90089, USA

    Joel Hay

Authors
  1. James R. Spalding
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joel Hay
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Joel Hay.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Spalding, J.R., Hay, J. Cost Effectiveness of Tumour Necrosis Factor-α Inhibitors as First-Line Agents in Rheumatoid Arthritis. Pharmacoeconomics 24, 1221–1232 (2006). https://doi.org/10.2165/00019053-200624120-00006

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00019053-200624120-00006

Keywords

Search

Navigation