Skip to main content
SpringerLink
Log in

Pursuit of optimal outcomes in rheumatoid arthritis

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

Abstract

The aim of this review is to describe methods of quantifying disease activity and symptomatology and discuss treatment goals for rheumatoid arthritis (RA). The benefits and limitations of existing therapeutic approaches, the importance of early therapy in preventing disease progression and the place of biologicals in early therapy will be discussed.

Disease activity and symptomatology in RA are often measured using a set of core endpoints that incorporate pain, patient global assessment, physical disability, swollen joints, tender joints, acute phase reactants, physician global assessment and radiographic imaging of joints. Imaging of joints is the only means by which to measure the effects of disease-modifying antirheumatic drugs (DMARDs) on the irreversible joint damage that occurs during RA. There is increasing evidence that this damage and its functional consequences occur early in the onset of disease. The consensus is that patients with RA should be treated with DMARDs earlier rather than later in the disease process. Remission, or a state of sustained response or low disease activity that is not damaging or disabling, is the ideal goal of therapy for RA, but formal criteria defining a state of remission need to be revised and, ideally, updated to include a radiographic component. Currently available DMARDs are limited in their ability to achieve early, sustained response or remission, by delayed onset of action, cumulative toxicity and lack of long-term therapeutic response. It is hoped that the emergence of novel DMARDs—targeted biological agents, such as anti-tumour necrosis factor-α (anti-TNF-α)—will help to counteract such limitations and will allow early DMARD use to be adopted as standard practice in place of their use as a last resort therapy after failure of other treatment. One such biological agent, etanercept, has been shown to reduce radiographic disease progression and induce overall clinical response during the early stages of RA. It is significantly more effective and fast-acting than methotrexate, one of the most effective, commonly used DMARDs.

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
Table III
Table IV
Fig. 1
Table V

Similar content being viewed by others

References

  1. Felson DT, Anderson JJ, Boers M, et al. American College of Rheumatology preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum 1995; 38 (6): 727–35

    Article  PubMed  CAS  Google Scholar 

  2. Tugwell P, Boers M, Baker P, et al. Endpoints in rheumatoid arthritis. J Rheumatol 1994; 21 Suppl. 42: 2–8

    Google Scholar 

  3. Felson DT, Anderson JJ, R.F. M. Time for changes in the design, analysis, and reporting of rheumatoid arthritis clinical trials. Arthritis Rheum 1990; 33 (1): 140–9

    Article  PubMed  CAS  Google Scholar 

  4. Tugwell P, Boers M. OMERACT conference on outcome measures in rheumatoid arthritis clinical trials: introduction. J Rheumatol 1993; 20 (3): 528–30

    PubMed  CAS  Google Scholar 

  5. Boers M, Tugwell P, Felson DT, et al. World Health Organization and International League of Associations for Rheumatology core endpoints for symptom modifying antirheumatic drugs in rheumatoid arthritis clinical trials. J Rheumatol 1994; 21 Suppl. 41: 86–9

    Google Scholar 

  6. Boers M, Brooks P, Strand V, et al. OMERACT IV: Fourth International Consensus Conference on Outcome Measures in Rheumatology. J Rheumatol 1999; 26 (1): 199–200

    Google Scholar 

  7. van der Heijde D, Boers M, Lassere M. Methodological issues in radiographic scoring methods in rheumatoid arthritis. J Rheumatol 1999; 26 (3): 726–30

    PubMed  Google Scholar 

  8. Larsen A., Dale K, Eek M. Radiographic evaluation of rheumatoid arthritis and related conditions by standard reference films. Acta Radiologica: Diagnosis 1977; 18: 481–91

    CAS  Google Scholar 

  9. Sharp JT, Lidsky MD, Collins LC, et al. Methods of scoring the progression of radiologic changes in rheumatoid arthritis: correlation of radiologic, clinical and laboratory abnormalities. Arthritis Rheum 1971; 14: 706–20

    Article  PubMed  CAS  Google Scholar 

  10. Plant MJ, Saklatvala J, Borg AA, et al. Measurement and prediction of radiological progression in early rheumatoid arthritis. J Rheumatol 1994; 21 (10): 1808–13

    PubMed  CAS  Google Scholar 

  11. Drossaers-Bakker KW, De Buck M, van Zeben D, et al. Long-term course and outcome of functional capacity in rheumatoid arthritis: the effect of disease activity and radiologic damage over time. Arthritis Rheum 1999; 42 (9): 1854–60

    Article  PubMed  CAS  Google Scholar 

  12. Gordon P, West J, Jones H, et al. A 10 year prospective followup of patients with rheumatoid arthritis 1986–96. J Rheumatol 2001; 28 (11): 2409–15

    PubMed  CAS  Google Scholar 

  13. Kirwan JR. Links between radiological change, disability, and pathology in rheumatoid arthritis. J Rheumatol 2001; 28 (4): 881–6

    PubMed  CAS  Google Scholar 

  14. Scott DL, Pugner K, Kaarela K, et al. The links between joint damage and disability in rheumatoid arthritis. Rheumatology 2000; 39 (2): 122–32

    Article  PubMed  CAS  Google Scholar 

  15. van der Heijde D. Radiographic progression in rheumatoid arthritis: does it reflect outcome? Does it reflect treatment? Ann Rheum Dis 2001; 60: iii47–50

    PubMed  Google Scholar 

  16. Kirwan JR. Conceptual issues in scoring radiographic progression in rheumatoid arthritis. J Rheumatol 1999; 26 (3): 720–5

    PubMed  CAS  Google Scholar 

  17. Bruynesteyn K, van der Heijde D, Boers M, et al. Determination of the minimal clinically important difference in rheumatoid arthritis joint damage of the Sharp/van der Heijde and Larsen/Scott scoring methods by clinical experts and comparison with the smallest detectable difference. Arthritis Rheum 2002; 46 (4): 913–20

    Article  PubMed  Google Scholar 

  18. Lassere M, Boers M, van der Heijde D, et al. Smallest detectable difference in radiological progression. J Rheumatol 1999; 26 (3): 731–9

    PubMed  CAS  Google Scholar 

  19. van der Heijde D, Lassere M, Edmonds J, et al. Minimal clinically important difference in plain films in RA: group discussions, conclusions and recommendations. J Rheumatol 2001; 28 (4): 914–7

    PubMed  Google Scholar 

  20. Felson DT, Anderson JJ, Lange ML, et al. Should improvement in rheumatoid arthritis clinical trials be defined as fifty percent or seventy percent improvement in core set measures, rather than twenty percent? Arthritis Rheum 1998; 41 (9): 1564–70

    PubMed  CAS  Google Scholar 

  21. van Gestel AM, Prevoo MLL, 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 

  22. van der Heijde DMFM, van’t Hof MA, van Riel PLCM, et al. Development of a disease activity score based on judgment in clinical practice by rheumatologists. J Rheumatol 1993; 20 (3): 579–81

    PubMed  Google Scholar 

  23. van Gestel AM, Anderson JJ, van Riel PL, et al. ACR and EULAR improvement criteria have comparable validity in rheumatoid arthritis trials. American College of Rheumatology European League of Associations for Rheumatology. J Rheumatol 1999; 26 (3): 705–11

    PubMed  Google Scholar 

  24. Ware Jr JE, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 1992; 30 (6): 473–83

    Article  PubMed  Google Scholar 

  25. Ware JE, Jr., Keller SD, Hatoum HT, et al. The SF-36 Arthritis-Specific Health Index (ASHI): I. Development and crossvalidation of scoring algorithms. Med Care 1999; 37 Suppl. 5: MS40–50

    Article  PubMed  Google Scholar 

  26. Pinals RS, Masi AT, Larsen RA. Preliminary criteria for clinical remission in rheumatoid arthritis. Arthritis Rheum 1981; 24 (10): 1308–15

    Article  PubMed  CAS  Google Scholar 

  27. Prevoo ML, van Gestel AM, van THMA, et al. Remission in a prospective study of patients with rheumatoid arthritis. American Rheumatism Association preliminary remission criteria in relation to the disease activity score. Br J Rheumatol 1996; 35 (11): 1101–5

    Article  PubMed  CAS  Google Scholar 

  28. Mottonen T, Hannonen P, Leirisalo-Repo M, et al. Comparison of combination therapy with single-drug therapy in early rheumatoid arthritis: a randomised trial. FIN-RACo trial group. Lancet 1999; 353 (9164): 1568–73

    Article  PubMed  CAS  Google Scholar 

  29. Teir J, Gray J, Pendlebury A, et al. Outcome of patients with early rheumatoid arthritis over a two year period. Ann Rheum Dis 1999; 58 (5): 323

    Article  PubMed  CAS  Google Scholar 

  30. Mottonen T, Paimela L, Leirisalo-Repo M, et al. Only high disease activity and positive rheumatoid factor indicate poor prognosis in patients with early rheumatoid arthritis treated with “sawtooth” strategy. Ann Rheum Dis 1998; 57 (9): 533–9

    Article  PubMed  CAS  Google Scholar 

  31. Svensson B, Schaufelberger C, Teleman A, et al. Remission and response to early treatment of RA assessed by the Disease Activity Score. BARFOT study group. Better Anti-rheumatic Farmacotherapy. Rheumatology (Oxford) 2000; 39 (9): 1031–6

    Article  CAS  Google Scholar 

  32. American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines, Guidelines for the management of rheumatoid arthritis. 2002 update. Arthritis Rheum 2002; 46 (2): 328–46

    Google Scholar 

  33. Felson 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 (10): 1117–25

    Article  PubMed  CAS  Google Scholar 

  34. Felson DT, Anderson JJ, Meenan RF. The comparative efficacy and toxicity of second-line drugs in rheumatoid arthritis. Results of two metaanalyses. Arthritis Rheum 1990; 33 (10): 1449–61

    Article  PubMed  CAS  Google Scholar 

  35. Papadopoulos NG, Alamanos Y, Papadopoulos IA, et al. Disease modifying antirheumatic drugs in early rheumatoid arthritis: a longterm observational study. J Rheumatol 2002; 29 (2): 261–6

    PubMed  CAS  Google Scholar 

  36. Pincus T, Marcum SB, Callahan FL. Longterm drug therapy for rheumatoid arthritis in seven rheumatology private practices: II. Second line drugs and prednisone. J Rheumatol 1992; 19 (12): 1885–94

    PubMed  CAS  Google Scholar 

  37. Bensen WG, Bensen W, Adachi JD. Back to the future: the pyramids of rheumatoid arthritis. J Rheumatol 1997; 24 (6): 1023–7

    PubMed  CAS  Google Scholar 

  38. Fries JF. Current treatment paradigms in rheumatoid arthritis. Rheumatology (Oxford) 2000; 39 Suppl. 1: 30–5

    Article  Google Scholar 

  39. Wolfe F, Rehman Q, Lane NE, et al. Starting a disease modifying antirheumatic drug or a biologic agent in rheumatoid arthritis: standards of practice for RA treatment. J Rheumatol 2001; 28 (7): 1704–11

    PubMed  CAS  Google Scholar 

  40. Fries JF. Reevaluating the therapeutic approach to rheumatoid arthritis: the “sawtooth” strategy. J Rheumatol 1990; 17 Suppl. 22: 12–5

    Google Scholar 

  41. Ward MM, Fries JF. Trends in antirheumatic medication use among patients with rheumatoid arthritis, 1981–1996. J Rheumatol 1998; 25 (3): 408–16

    PubMed  CAS  Google Scholar 

  42. Irvine S, Munro R, Porter D. Early referral, diagnosis, and treatment of rheumatoid arthritis: evidence for changing medical practice. Ann Rheum Dis 1999; 58 (8): 510–3

    Article  PubMed  CAS  Google Scholar 

  43. Sokka TM, Kaarela K, Mottonen TT, et al. Conventional monotherapy compared to a “sawtooth” treatment strategy in the radiographic progression of rheumatoid arthritis over the first eight years. Clin Exp Rheumatol 1999; 17 (5): 527–32

    PubMed  CAS  Google Scholar 

  44. Sokka T, Mottonen T, Hannonen P. Disease-modifying antirheumatic drug use according to the ’sawtooth’ treatment strategy improves the functional outcome in rheumatoid arthritis: results of a long-term follow-up study with review of the literature. Rheumatology (Oxford) 2000; 39 (1): 34–42

    Article  CAS  Google Scholar 

  45. Pincus T, O’Dell JR, Kremer JM. Combination therapy with multiple disease-modifying antirheumatic drugs in rheumatoid arthritis: a preventative strategy. Ann Intern Med 1999; 131 (10): 768–74

    PubMed  CAS  Google Scholar 

  46. Pincus T, Callahan LF, Sale WG, et al. Severe functional declines, work disability, and increased mortality in seventyfive rheumatoid arthritis patients studied over nine years. Arthritis Rheum 1984; 27 (8): 864–72

    Article  PubMed  CAS  Google Scholar 

  47. Fries JF, Williams CA, Ramey D, et al. The relative toxicity of disease-modifying antirheumatic drugs. Arthritis Rheum 1993; 36 (3): 297–306

    Article  PubMed  CAS  Google Scholar 

  48. Simon LS, Yocum D. New and future drug therapies for rheumatoid arthritis. Rheumatology (Oxford) 2000; 39 Suppl. 1: 36–42

    Article  CAS  Google Scholar 

  49. Simon LS. DMARDs in the treatment of rheumatoid arthritis: current agents and future developments. Int J Clin Pract 2000; 54 (4): 243–9

    PubMed  CAS  Google Scholar 

  50. Fuchs HA, Kaye JJ, Callahan LF, et al. Evidence of significant radiographic damage in rheumatoid arthritis within the first 2 years of disease. J Rheumatol 1989; 16 (5): 585–91

    PubMed  CAS  Google Scholar 

  51. Brook A, Corbett M. Radiographic changes in early rheumatoid disease. Ann Rheum Dis 1977; 36 (1): 71–3

    Article  PubMed  CAS  Google Scholar 

  52. McGonagle D, Conaghan PG, O’Connor P, et al. The relationship between synovitis and bone changes in early untreated rheumatoid arthritis. A controlled magnetic resonance imaging study. Arthritis Rheum 1999; 42 (8): 1706–11

    Article  PubMed  CAS  Google Scholar 

  53. Emery P. Evidence supporting the benefit of early intervention in rheumatoid arthritis. J Rheumatol 2002; 29 Suppl. 66: 3–8

    Google Scholar 

  54. Yelin E, Trupin L, Wong B, et al. The impact of functional status and change in functional status on mortality over 18 years among persons with rheumatoid arthritis. J Rheumatol 2002; 29 (9): 1851–7

    PubMed  Google Scholar 

  55. Doeglas D, Suurmeijer T, Krol B, et al. Work disability in early rheumatoid arthritis. Ann Rheum Dis 1995; 54 (6): 455–60

    Article  PubMed  CAS  Google Scholar 

  56. Eberhardt K, Larsson BM, Nived K. Early rheumatoid arthritis—some social economical, and psychological aspects. Scand J Rheumatol 1993; 22 (3): 119–23

    Article  PubMed  CAS  Google Scholar 

  57. Fex E, Larsson B-M, Nived K, et al. Effect of rheumatoid arthritis on work status and social and leisure time activities in patients followed 8 years from onset. J Rheumatol 1998; 25 (1): 44–50

    PubMed  CAS  Google Scholar 

  58. Egsmose C, Lund B, Borg G, et al. Patients with rheumatoid arthritis benefit from early 2nd line therapy: 5 year followup of a prospective double blind placebo controlled study. J Rheumatol 1995; 22 (12): 2208–13

    PubMed  CAS  Google Scholar 

  59. Stenger AA, Van Leeuwen MA, Houtman PM, et al. Early versus delayed treatment in patients with recent-onset rheumatoid arthritis: comparison of two cohorts who received different treatment strategies. Am J Med 2001; 111 (6): 446–51

    Article  Google Scholar 

  60. Lard LR, Visser H, Speyer I, et al. Early effective suppression of inflammation in rheumatoid arthritis reduces radiographic progression. Br J Rheumatol 1998; 37 (11): 1157–63

    Article  Google Scholar 

  61. van der Heide A, Jacobs JW, Bijlsma JW, et al. The effectiveness of early treatment with “second-line” antirheumatic drugs. A randomized, controlled trial. Ann Intern Med 1996; 124 (8): 699–707

    PubMed  Google Scholar 

  62. Tsakonas E, Fitzgerald AA, Fitzcharles MA, et al. Consequences of delayed therapy with second-line agents in rheumatoid arthritis: a 3 year followup on the hydroxychloroquine in early rheumatoid arthritis (HERA) study. J Rheumatol 2000; 27 (3): 623–9

    PubMed  CAS  Google Scholar 

  63. Furst DE, Breedveld FC, Burmester GR, et al. Updated consensus statement on tumour necrosis factor blocking agents for the treatment of rheumatoid arthritis (May 2000). Ann Rheum Dis 2000; 59 Suppl. 1: i1–2

    Article  PubMed  Google Scholar 

  64. Smolen JS, Breedveld FC, Burmester GR, et al. Consensus statement on the initiation and continuation of tumour necrosis factor blocking therapies in rheumatoid arthritis. Ann Rheum Dis 2000; 59 (7): 504–5

    Article  PubMed  CAS  Google Scholar 

  65. 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 (22): 1586–93

    Article  PubMed  CAS  Google Scholar 

  66. Keystone E, Furst DE, Kavanaugh AF, et al. Subgroup analysis of radiographic progression in RA patients treated with adalimumab [abstract]. in EULAR. 2003; Lisbon, Portugal

    Google Scholar 

  67. van de Putte LBA, Rau R, Breedveld FC, et al. One year efficacy results of the fully human anti-TNF antibody D2E7 in rheumatoid arthritis [abstract]. Arthritis Rheum 2000; 43 Suppl.: 269

    Google Scholar 

  68. Lipsky PE, van der Heijde DM, St Clair EW, et al. Anti-tumor necrosis factor trial in rheumatoid arthritis with concomitant therapy study group. N Engl J Med 2000; 343 (22): 1594–602

    Article  PubMed  CAS  Google Scholar 

  69. Genovese MC, Martin RW, Fleischmann RM, et al. Etanercept in early erosive rheumatoid arthritis (ERA trial): 4-year clinical and radiographic data. in EULAR. 2003; Lisbon, Portugal

    Google Scholar 

  70. Boers M, Verhoeven AC, Markusse HM, et al. Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis. Lancet 1997; 350 (9074): 309–18. Erratum in: Lancet 1998; 351 (9097): 220

    Article  PubMed  CAS  Google Scholar 

  71. 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 

  72. Maini RN, Breedveld FC, Kalden JR, et al. Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis. Arthritis Rheum 1998; 41 (9): 1552–1563

    Article  PubMed  CAS  Google Scholar 

  73. Maini R, St Clair EW, Breedveld F, et al. Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. ATTRACT Study Group. Lancet 1999; 354 (9194): 1932–9

    Article  PubMed  CAS  Google Scholar 

  74. 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 

  75. Kavanaugh A, St Clair EW, McCune WJ, et al. Chimeric antitumor necrosis factor-alpha monoclonal antibody treatment of patients with rheumatoid arthritis receiving methotrexate therapy. J Rheumatol 2000; 27 (4): 841–50

    PubMed  CAS  Google Scholar 

Download references

Acknowlegement

This study was supported by a grant from Wyeth.

Author information

Authors and Affiliations

  1. King’s College Hospital, London, England

    David L. Scott (Professor of Clinical Rheumatology)

Authors
  1. David L. Scott
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David L. Scott.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Scott, D.L. Pursuit of optimal outcomes in rheumatoid arthritis. Pharmacoeconomic 22 (Suppl 1), 13–26 (2004). https://doi.org/10.2165/00019053-200422001-00003

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00019053-200422001-00003

Keywords

Search

Navigation