Skip to main content
SpringerLink
Log in

Long-Term Experience with Etanercept in the Treatment of Rheumatoid Arthritis in Elderly and Younger Patients

Patient-Reported Outcomes from Multiple Controlled and Open-Label Extension Studies

  • Original Research Article
  • Published:
Drugs & Aging Aims and scope Submit manuscript

Abstract

Background

The impact of long-term therapy for rheumatoid arthritis (RA) in elderly (≥65 years of age) and younger (<65 years of age) patients, especially on patient-reported outcomes, has not been well studied. We evaluated patient-reported outcomes in elderly patients treated with etanercept, in contrast to outcomes in younger patients, using data from multiple controlled and open-label extension studies of patients with early RA (ERA; ≤3 years) and late RA (LRA; disease-modifying antirheumatic drug [DMARD]-refractory RA).

Methods

This post hoc analysis included adult patients with RA enrolled in controlled, double-blind studies (up to 2 years) and subsequent open-label extension studies (up to 4 years). Patients were evaluated according to age at baseline of the original study. Patients may have received etanercept, placebo or methotrexate during the blinded treatment phases, but all patients had been receiving etanercept 25mg twice weekly for at least 4 years. Both ERA and LRA extension studies are ongoing. Patient-reported outcome assessments included improvement in Health Assessment Questionnaire — Disability Index (HAQ-DI), proportions of patients achieving an improvement in HAQ-DI ≥0.22 points, patients exhibiting worsening of HAQ-DI and patients achieving an HAQ-DI score of 0.

Results

Elderly patients, with either ERA or LRA, had significantly worse baseline mean HAQ-DI scores than younger patients (p < 0.05, Student’s t-test) in most studies, indicating greater disability. Improvement in HAQ-DI was greatest during the first 3 months after starting etanercept treatment in the controlled phase and appeared to be sustained over 3–6 months in patients with early or DMARD-refractory RA. Across the various controlled trials, mean improvements from baseline in HAQ-DI ranged from 0.39 to 0.92 points in elderly patients and from 0.57 to 1.00 points in younger patients. Patients with ERA and LRA, regardless of age group, maintained their improvement in HAQ-DI throughout the open-label extension trials for up to a total of 6 years of etanercept therapy. Change from baseline in HAQ-DI was moderately correlated with 28-joint Disease Activity Score within each age group across the multiple trials.

Conclusion

Both elderly and younger patients with RA treated with etanercept exhibited similar and rapid improvements in functional status during controlled studies, and these improvements were sustained during open-label extension trials.

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
Table II
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Table III

Similar content being viewed by others

References

  1. Schiff M. A rationale for the use of summary measurements for the assessment of the effects of rheumatoid arthritis therapies. Clin Ther 2003; 25(3): 993–1001

    Article  PubMed  Google Scholar 

  2. Lee DM, Weinblatt ME. Rheumatoid arthritis. Lancet 2001; 358: 903–11

    Article  PubMed  CAS  Google Scholar 

  3. Fleischmann RM, Baumgartner SW, Tindall EA, et al. Response to etanercept (enbrel) in elderly patients with rheumatoid arthritis: a retrospective analysis of clinical trial results. J Rheumatol 2003; 30(4): 691–6

    PubMed  CAS  Google Scholar 

  4. Papadopoulos IA, Katsimbri P, Alamanos Y, et al. Early rheumatoid arthritis patients: relationship of age. Rheumatol Int 2003; 23(2): 70–4

    PubMed  Google Scholar 

  5. Mitchell DM. Rheumatoid arthritis: etiology, diagnosis, management. In: Ehrlich GE, Zvaifler NJ, Utsinger PD, editors. Epidemiology. Philadelphia (PA): JB Lippincott, 1985: 1333–7

    Google Scholar 

  6. Robinson H. Arthritis and the elderly. In: Moskowitz M, editor. Multidisciplinary ambulatory care for the elderly arthritis patients. New York: Springer, 1986: 146–9

    Google Scholar 

  7. Moreland LW, Schiff MH, Baumgartner SW, et al. Etanercept therapy in rheumatoid arthritis: a randomized, controlled trial. Ann Intern Med 1999; 130(6): 478–86

    PubMed  CAS  Google Scholar 

  8. Weinblatt ME, Kremer JM, Bankhurst AD, et al. A trial of etanercept, a recombinant tumor necrosis factor receptor: Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. N Engl J Med 1999; 340(4): 253–9

    Article  PubMed  CAS  Google Scholar 

  9. Bathon JM, Martin RW, Fleischmann RM, et al. A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis [published erratum appears in N Engl J Med 2001; 344 (3): 240]. N Engl J Med 2000; 343(22): 1586–93

    Article  PubMed  CAS  Google Scholar 

  10. Genovese MC, Bathon JM, Martin RW, et al. Etanercept versus methotrexate in patients with early rheumatoid arthritis: two-year radiographic and clinical outcomes. Arthritis Rheum 2002; 46(6): 1443–50

    Article  PubMed  CAS  Google Scholar 

  11. Klareskog L, van der Heijde D, de Jager JP, 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(9410): 675–81

    Article  PubMed  CAS  Google Scholar 

  12. 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(6): 1209–18

    Article  PubMed  CAS  Google Scholar 

  13. Wolfe F, Michaud K, Gefeller O, et al. Predicting mortality in patients with rheumatoid arthritis. Arthritis Rheum 2003; 48(6): 1530–42

    Article  PubMed  Google Scholar 

  14. Mathias SD, Colwell HH, Miller DP, et al. Health-related quality of life and functional status of patients with rheumatoid arthritis randomly assigned to receive etanercept or placebo. Clin Ther 2000; 22(1): 128–39

    Article  PubMed  CAS  Google Scholar 

  15. Kosinski M, Kujawski SC, Martin R, et al. Health-related quality of life in early rheumatoid arthritis: impact of disease and treatment response. Am J Manag Care 2002; 8(3): 231–40

    PubMed  Google Scholar 

  16. Baumgartner SW, Fleischmann RM, Moreland LW, et al. Etanercept (Enbrel) in patients with rheumatoid arthritis with recent onset versus established disease: improvement in disability. J Rheumatol 2004; 31(8): 1532–7

    PubMed  CAS  Google Scholar 

  17. Moreland LW, Cohen SB, Baumgartner SW, et al. Long-term safety and efficacy of etanercept in patients with rheumatoid arthritis. J Rheumatol 2001; 28(6): 1238–44

    PubMed  CAS  Google Scholar 

  18. Fries JF, Spitz P, Kraines RG, et al. Measurement of patient outcome in arthritis. Arthritis Rheum 1980; 23(2): 137–45

    Article  PubMed  CAS  Google Scholar 

  19. Bruce B, Fries JF. The Stanford Health Assessment Questionnaire: a review of its history, issues, progress, and documentation. J Rheumatol 2003; 30(1): 167–78

    PubMed  Google Scholar 

  20. Wells GA, Tugwell P, Kraag GR, et al. Minimum important difference between patients with rheumatoid arthritis: the patient’s perspective. J Rheumatol 1993; 20(3): 557–60

    PubMed  CAS  Google Scholar 

  21. Fries JF, Singh G, Morfeld D, et al. Running and the development of disability with age. Ann Intern Med 1994; 121(7): 502–9

    PubMed  CAS  Google Scholar 

  22. Hubert HB, Bloch DA, Fries JF. Risk factors for physical disability in an aging cohort: the NHANES I Epidemiologic Followup Study [published erratum appears in J Rheumatol 1994; 21 (1): 177]. J Rheumatol 1993; 20(3): 480–8

    PubMed  CAS  Google Scholar 

  23. Krishnan E, Sokka T, Hakkinen A, et al. Normative values for the Health Assessment Questionnaire disability index: benchmarking disability in the general population. Arthritis Rheum 2004; 50(3): 953–60

    Article  PubMed  Google Scholar 

  24. van Gestel AM, Prevoo ML, van’t Hof MA, et al. Development and validation of the European League Against Rheumatism response criteria for rheumatoid arthritis: comparison with the preliminary American College of Rheumatology and the World Health Organization/International League Against Rheumatism Criteria. Arthritis Rheum 1996; 39(1): 34–40

    Article  PubMed  Google Scholar 

  25. Prevoo ML, van’t Hof MA, Kuper HH, et al. Modified disease activity scores that include twenty-eight-joint counts: development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 1995; 38(1): 44–8

    Article  PubMed  CAS  Google Scholar 

  26. DAS-Score.nl. Disease activity scores using C-reactive protein. Department of Rheumatology, University Medical Centre, Nijmegan-The Netherlands [online]. Available from URL: http://www.reuma-nijmegen.nl/www.das-score.nl [Accessed 2006 Feb 14]

  27. Strand V, Scott DL, Emery P, et al. Physical function and health related quality of life: analysis of 2-year data from randomized, controlled studies of leflunomide, sulfasalazine, or methotrexate in patients with active rheumatoid arthritis. J Rheumatol 2005; 32(4): 590–601

    PubMed  CAS  Google Scholar 

  28. van der Heijde D, Klareskog L, Singh A, et al. Patient-reported outcomes in a trial of combination therapy with etanercept and methotrexate for rheumatoid arthritis: the TEMPO trial. Ann Rheum Dis. Epub 2005 Sept 28

  29. Keystone EC, Kavanaugh AF, Sharp JT, 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. Arthritis Rheum 2004; 50(5): 1400–11

    Article  PubMed  CAS  Google Scholar 

  30. St Clair EW, van der Heijde DM, Smolen JS, et al. Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial. Arthritis Rheum 2004; 50(11): 3432–43

    Article  PubMed  CAS  Google Scholar 

  31. Wolfe F, Michaud K, Strand V. Expanding the definition of clinical differences: from minimally clinically important differences to really important differences: analyses in 8931 patients with rheumatoid arthritis. J Rheumatol 2005; 32: 583–9

    PubMed  Google Scholar 

Download references

Acknowledgements

Research funded by Immunex Corporation, a wholly owned subsidiary of Amgen Inc., and by Wyeth. The authors would like to thank the patients, investigators and study site personnel who participated in the various clinical trials included in this analysis. The authors would also like to thank C.F. Chiou, PhD, for critically reviewing the manuscript and H. Wilfehrt, PhD, and S. Myers, MSc, for assistance in drafting this manuscript. The authors would like to note that Elaine Yu is now an employee of Genentech.

M.H. Schiff has received a research grant, consulted and participated on Speakers’ Bureaux for Abbott, Amgen, Aventis, Bristol-Myers Squibb, Centocor, Merck and Wyeth-Ayerst. M.H. Schiff has also received research grants and participated on the Speakers’ Bureau for Roche and consulted and participated on the Speakers’ Bureau for Novartis.

E.B. Yu was an employee of Amgen at the time the analyses and manuscript were completed.

M.E. Weinblatt received a research grant, consulted and participated on the Speakers’ Bureau for Amgen. M.E. Weinblatt has also acted as a consultant for Wyeth, Centocor, Bristol-Myers Squibb, Roche, Genentech, Abbott and Biogen/Idec.

L.W. Moreland has received research grants, consulted and participated on the Speakers’ Bureau for Amgen.

M.C. Genovese has received a research grant from and acted as a consultant for Amgen, Wyeth, Centocor and Abbott.

A. Singh, Y. Chon, B. White and J.M. Woolley are employees of Amgen.

Author information

Authors and Affiliations

  1. Denver Arthritis Clinic, University of Colorado, Denver, Colorado, USA

    Michael H. Schiff

  2. Amgen Inc., Thousand Oaks, California, USA

    Elaine B. Yu, Barbara White, Yun Chon & J. Michael Woolley

  3. Brigham and Women’s Hospital, Boston, Massachusetts, USA

    Michael E. Weinblatt

  4. University of Alabama at Birmingham, Birmingham, Alabama, USA

    Larry W. Moreland

  5. Stanford University Medical Center, Palo Alto, California, USA

    Mark C. Genovese

  6. Wyeth Research, Collegeville, Pennsylvania, USA

    Amitabh Singh

Authors
  1. Michael H. Schiff
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elaine B. Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael E. Weinblatt
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Larry W. Moreland
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mark C. Genovese
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Barbara White
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Amitabh Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yun Chon
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. J. Michael Woolley
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael H. Schiff.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schiff, M.H., Yu, E.B., Weinblatt, M.E. et al. Long-Term Experience with Etanercept in the Treatment of Rheumatoid Arthritis in Elderly and Younger Patients. Drugs Aging 23, 167–178 (2006). https://doi.org/10.2165/00002512-200623020-00006

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002512-200623020-00006

Keywords

Search

Navigation