Disease Management & Health Outcomes

, Volume 12, Issue 1, pp 1–8 | Cite as

Adalimumab for Rheumatoid Arthritis

Considerations for Reimbursement by Third-Party Payors
  • Leo van de Putte
  • Michael B. Nichol
Current Opinion


Third-party payors and national health systems require evidence that new medications for rheumatoid arthritis are cost effective. To determine cost effectiveness, one must consider the cost of a given therapy versus the long-term cost of the disease, with and without therapy. The direct and indirect costs of rheumatoid arthritis over the course of the disease, including the considerable costs related to hospitalization and disability, have been quantified. Resource utilization and treatment costs are high for patients with rheumatoid arthritis, and there is a strong link between functional disability and direct cost of care.

Traditional disease-modifying antirheumatic drugs (DMARDs) [such as methotrexate and gold] have limited long-term effects in improving lives and avoiding costs for patients with rheumatoid arthritis. Tumor necrosis factor (TNF) antagonists, the newest class of rheumatoid arthritis drug therapies, significantly improve patient outcomes, including reducing the signs and symptoms of rheumatoid arthritis, improving physical function and health-related quality of life, and inhibiting radiographie damage. Failing to treat rheumatoid arthritis effectively is very costly; effective treatment includes early, aggressive therapy. As a result, the National Health Service in the UK, other societal decision-makers, and third-party payors have recommended the use of TNF antagonists, in many instances, for the treatment of rheumatoid arthritis.

The TNF antagonists — infliximab, etanercept, and the most recently approved, adalimumab — address the limitations of traditional DMARDs, thus setting a new therapeutic standard for rheumatoid arthritis. Data from three key studies (Anti-TNF Research Program of the Monoclonal Antibody Adalimumab in Rheumatoid Arthritis, DE019 and DE011) indicate that adalimumab provides a rapid, sustainable, predictable, and significantly greater reduction in the signs and symptoms of rheumatoid arthritis than traditional DMARDs. Adalimumab yields significantly less structural joint damage as measured by the total Sharp scores and scores on its two major components: joint erosions and joint space narrowing. It also improves physical function (as measured by the Health Assessment Questionnaire Disability Index) and health utility (as measured by the Health Utilities Index Mark 3).

In conclusion, rheumatoid arthritis and other musculoskeletal diseases are costly, but an upfront investment in highly effective therapies may provide long-term cost savings compared with traditional therapies. The immediate, out-of-pocket costs of TNF antagonists are greater than traditional DMARDs, but with the potential to significantly improve response rates, inhibit structural joint damage, and improve disability and health utility, TNF antagonists have the potential to be more cost effective over the long run. TNF antagonists can be valuable for patients in need and therefore appropriate for reimbursement by national health systems and third-party payors.


Rheumatoid Arthritis Infliximab Etanercept Adalimumab Swell Joint Count 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



>We are paid consultants of Abbott Laboratories. In addition, we wish to thank Michael Nissen of the Biomedical Publishing Group of Abbott Laboratories for his editorial contributions to this article.


  1. 1.
    Felts W, Yelin E. The economic impact of the rheumatic diseases in the United States. J Rheumatol 1989; 16: 867–84PubMedGoogle Scholar
  2. 2.
    Yelin E, Henke C, Epstein W. The work dynamics of the person with rheumatoid arthritis. Arthritis Rheum 1987; 30: 507–12PubMedCrossRefGoogle Scholar
  3. 3.
    Sokka T, Kautiainen H, Mottonen T, et al. Work disability in rheumatoid arthritis 10 years after the diagnosis. J Rheumatol 1999; 26: 1681–5PubMedGoogle Scholar
  4. 4.
    O’Dell J. Conventional DMARD options for patients with a sub optimal response to methotrexate. Rheumatology 2001; 28: 21–6Google Scholar
  5. 5.
    Van der Heijde DMFM, van Leeuwen MA, van Riel PLCM, et al. Radiographic progression on radiographs of hands and feet during the first 3 years of RA measured according to Sharp’s method (van der Heijde modification). J Rheumatol 1995; 22: 1792–6PubMedGoogle Scholar
  6. 6.
    Yelin E, Wanke LA. An assessment of the annual and long-term direct costs of rheumatoid arthritis: the impact of poor function and functional decline. Arthritis Rheum 1999; 42: 1209–18PubMedCrossRefGoogle Scholar
  7. 7.
    Kobelt G, Eberhardt K, Jonsson L, et al. Economic consequences of the progression of rheumatoid arthritis in Sweden. Arthritis Rheum 1999; 42: 347–56PubMedCrossRefGoogle Scholar
  8. 8.
    Wolfe F, Zwillich SH. Long-term outcomes of rheumatoid arthritis: a 23 year prospective, longitudinal study of total joint replacement and its predictors in 1,600 patients with rheumatoid arthritis. Arthritis Rheum 1998; 41: 1072–82PubMedCrossRefGoogle Scholar
  9. 9.
    Ruof J, Hülsemann JL, Mittendorf T. Costs of rheumatoid arthritis in Germany: a micro-costing approach based on healthcare payer’s data sources. Ann Rheum Dis 2003; 62: 544–50PubMedCrossRefGoogle Scholar
  10. 10.
    Morand EF, McCloud PI, Littlejohn GO. Life table analysis of 879 treatment episodes with slow acting antirheumatic drugs in community rheumatology practice. J Rheumatol 1992; 19: 704–8PubMedGoogle Scholar
  11. 11.
    Pincus T, Marcum SB, Callahan LF. Long term drug therapy for rheumatoid arthritis in seven rheumatology private practices: II. second line drugs and prednisone. J Rheumatol 1992; 19: 1885–94PubMedGoogle Scholar
  12. 12.
    Felsen DT, Anderson JJ, Meenan RF. Use of short-term efficacy/toxicity tradeoffs to select second-line drugs in rheumatoid arthritis: a metaanalysis of published clinical trials. Arthritis Rheum 1992; 35: 1117–25CrossRefGoogle Scholar
  13. 13.
    National Institute for Clinical Excellence. Technology Appraisal Guidance—No. 36: guidance on the use of etanercept and infliximab for the treatment of rheumatoid arthritis. 2002 MarGoogle Scholar
  14. 14.
    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: 326–35PubMedCrossRefGoogle Scholar
  15. 15.
    Bathon JM, Martin RW, Fleischmann RM, et al. A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med 2000; 343: 1586–93PubMedCrossRefGoogle Scholar
  16. 16.
    Lipsky PE, van der Heijde DM, St Clair EW, et al. Infliximab and methotrexate in the treatment of rheumatoid arthritis: Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group. N Engl J Med 2000; 343: 1594–602PubMedCrossRefGoogle Scholar
  17. 17.
    Van de Putte L, Bergemann R, Rosery H, et al. Variation in resource utilization and treatment costs for rheumatoid arthritis (RA) across 5 countries in an adalimumab (D2E7) clinical trial [abstract]. Value Health 2002; 5(6): 461CrossRefGoogle Scholar
  18. 18.
    Hunsche E, Chancellor JV, Bruce N. The burden of arthritis and nonsteroidal anti-inflammatory treatment: a European literature review. Pharmacoeconomics 2001; 9 Suppl. 1: 1–15CrossRefGoogle Scholar
  19. 19.
    Leardini G, Salaffi F, Montanelli R, et al. A multicenter cost-of-illness study on rheumatoid arthritis in Italy. Clin Exp Rheumatol 2002; 20: 505–15PubMedGoogle Scholar
  20. 20.
    Breedveld FC, Rau R, van Riel PLC. Sustained efficacy over 5 years with adalimumab (HUMIRA®) in patients with active rheumatoid arthritis [abstract]. Arthritis Rheum 2003; 48(9): S118Google Scholar
  21. 21.
    van de Putte LBA, Rau R, Burmester GR. Sustained 5-year efficacy of adalimumab (HUMIRA®) monotherapy in DMARD-refractory rheumatoid arthritis (RA) [abstract]. Arthritis Rheum 2003; 48(9): S314Google Scholar
  22. 22.
    Weinblatt ME, Keystone EC, Furst DE, et al. Adalimumab, a fully human anti-tumor necrosis factor α monoclonal antibody for the treatment of RA in patients taking concomitant methotrexate: The ARMADA trial. Arthritis Rheum 2003; 48: 35–45PubMedCrossRefGoogle Scholar
  23. 23.
    Keystone EC, Kavanaugh AF, Sharp JT, et al. Radiographic, clinical, and functional outcomes with adalimumab (a human anti-TNF monoclonal antibody) in the treatment of patients with active rheumatoid arthritis on concomitant methotrexate therapy: a randomized, placebo-controlled, 52-week trial. Arthritis Rheum. In pressGoogle Scholar
  24. 24.
    Weinblatt ME, Keystone EC, Furst DE, et al. The ARMADA Trial: sustained improvement and tolerability in long-term follow-up of patients treated with adalimumab (HUMIRA®) [poster presentation]. American College of Rheumatology 2003 annual conference 2003 Oct 26, Orlando (FL)Google Scholar
  25. 25.
    Van de Putte LBA, Atkins C, Malaise M, et al. Adalimumab (D2E7) monotherapy in the treatment of patients with severely active rheumatoid arthritis [abstract]. Arthritis Rheum 2002; 46 Suppl.: S205Google Scholar
  26. 26.
    Keystone EC, Kavanaugh A, Sharp J. Sustained radiographie inhibition with adalimumab (HUMIRA®) over 2 years in patients with long-standing rheumatoid arthritis (RA) [poster presentation]. American College of Rheumatology 2003 annual conference 2003 Oct 26, Orlando (FL)Google Scholar
  27. 27.
    Pincus T, Brook RH, Callahan LF, et al. Prediction of long-term mortality in patients with rheumatoid arthritis according to simple questionnaire and joint count measures. Ann Intern Med 1994; 120: 25–4Google Scholar
  28. 28.
    Goldsmith CH, Boers M, Bombardier C, et al. Criteria for clinically important changes in outcomes: development, scoring and evaluation of rheumatoid arthritis patient and trial profiles. OMERACT Committee. J Rheumatol 1993; 20: 561–5PubMedGoogle Scholar
  29. 29.
    Van de Putte L, Boggs R, Sengupta N, et al. Improvement in health utility among rheumatoid arthritis (RA) patients treated with adalimumab (D2E7), a fully human anti-TNF monoclonal antibody [abstract]. Value Health 2002; 5(6): 461CrossRefGoogle Scholar
  30. 30.
    FDA Arthritis Advisory Committee Reports [online]. 2003 Mar 4. Available from URL: [Accessed 2003 Dec 23]
  31. 31.
    Bansback NJ, Brennan A, Ghatekar O, et al. The cost effectiveness of adalimumab (HUMIRA®) in patients with rheumatoid arthritis (RA): a Swedish analysis [poster presentation]. American College of Rheumatology 2003 annual conference 2003 Oct 27, Orlando (FL)Google Scholar
  32. 32.
    Bansback NJ, Brennan A, Sengupta N, et al. Cost effectiveness of adalimumab (HUMIRA®) in the treatment of patients with moderate to severe rheumatoid arthritis (RA) [poster presentation]. American College of Rheumatology 2003 annual conference 2003 Oct 25, Orlando (FL)Google Scholar

Copyright information

© Adis Data Information BV 2004

Authors and Affiliations

  1. 1.Department of RheumatologyUniversity HospitalNijmegenThe Netherlands
  2. 2.Department of Pharmaceutical Economics and Policy, School of PharmacyUniversity of Southern CaliforniaLos AngelesUSA

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