Current Rheumatology Reports

, Volume 5, Issue 4, pp 287–293 | Cite as

Early rheumatoid arthritis: Toward tailor-made therapy

  • Robert B. M. Landewé
  • Désirée M. F. M. van der Heijde


Therapeutic possibilities for the treatment of early rheuma-toid arthritis (RA) have expanded largely. New treatment modalities appear very effective with respect to relevant outcomes, such as radiographic progression. At the same time, the costs of disease-modifying antirheumatic drugs (DMARDs) have exponentially increased so that—given the rather high prevalence of RA—cost may become a limiting factor in the treatment of patients with RA. Therefore, there is a need to define the profile of those patients that should be treated with the most effective, and, unfortu-nately, the most costly, DMARDs. The authors describe herewith the heterogeneity of RA with respect to its most important outcomes, as well as the inability to predict those outcomes appropriately at the individual patient level. This heterogeneity of RA is not acknowledged in the mod-ern landmark clinical trials that the authors base therapeu-tic decisions on, and the external validity of those trials is at stake. In this article, the authors discuss the consequences of the heterogeneity of RA in light of the perceived lack of external validity of evidence-generating landmark trials. The authors propose the following solutions to overcome this discrepancy: 1) earlier recognition of RA, and 2) appropri-ate prediction of treatment efficacy, because the most chal-lenging scientific efforts may be taken in the near future in order to arrive at a tailor-made therapy for every individual presenting with RA.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    van der Horst-Bruinsma I.E.: Diagnosis and course of early-onset arthritis: results of a special early arthritis clinic compared to routine patient care. Br J Rheumatol 1998, 37:1084–1088. References [1 ], [2 ], and [3 ] are examples from early arthritis clinics (the Leiden early arthritis clinic [1 ], the Vienna early arthritis clinic [2 ], and the Norfolk Arthritis Register [3 ]), with a slightly different spectrum of patients included.PubMedCrossRefGoogle Scholar
  2. 2.
    Machold KP: Very recent onset arthritis: clinical, laboratory, and radiological findings during the first year of disease. J Rheumatol 2002, 29:2278. References [1 ], [2 ], and [3 ] are examples from early arthritis clinics (the Leiden early arthritis clinic [1 ], the Vienna early arthritis clinic [2 ], and the Norfolk Arthritis Register [3 ]), with a slightly different spectrum of patients included.PubMedGoogle Scholar
  3. 3.
    Harrison B: Early inflammatory polyarthritis: results from the Norfolk Arthritis Register with a review of the literature, II: outcome at three years. A simple algorithm to predict the development of radiological erosions in patients with early rheumatoid arthritis: prospective cohort study. Measuring outcome in rheumatoid arthritis: which measures are suit-able for routine clinical use? Rheumatology 2000, 39:939–949. References [1 ], [2 ], and [3 ] are examples from early arthritis clinics (the Leiden early arthritis clinic [1 ], the Vienna early arthritis clinic [2 ], and the Norfolk Arthritis Register [3 ]), with a slightly different spectrum of patients included.PubMedCrossRefGoogle Scholar
  4. 4.
    Visser H: How to diagnose rheumatoid arthritis early: a pre-diction model for persistent (erosive) arthritis. Arthritis Rheum 2002, 46:357–365. Prediction algorithm for persistence and erosiveness for patients pre-senting with early arthritis. Unlike many other prognostic studies, this one is from the perspective of the individual patient.PubMedCrossRefGoogle Scholar
  5. 5.
    Pincus T, Callahan LF: Early mortality in RA predicted by poor clinical status. Bull Rheum Dis 1992, 41:1–4.PubMedGoogle Scholar
  6. 6.
    Rasker JJ, Cosh JA: The natural history of rheumatoid arthritis over 20 years: clinical symptoms, radiological signs, treat-ment, mortality and prognostic significance of early features. Clin Rheumatol 1987, 6(suppl):5–11.PubMedCrossRefGoogle Scholar
  7. 7.
    Katusic S: Occurrence of malignant neoplasms in the Roches-ter, Minnesota, rheumatoid arthritis cohort. Am J Med 1985, 78:50–55.PubMedCrossRefGoogle Scholar
  8. 8.
    van der Heijde DM: Biannual radiographic assessments of hands and feet in a three-year prospective followup of patients with early rheumatoid arthritis. Arthritis Rheum 1992, 35:26–34.PubMedCrossRefGoogle Scholar
  9. 9.
    Wluka A: Long-term methotrexate use in rheumatoid arthri-tis: 12 year followup of 460 patients treated in community practice. J Rheumatol 2000, 27:1864–1871.PubMedGoogle Scholar
  10. 10.
    Wol f e F: The mortality of rheumatoid arthritis. Arthritis Rheum 1994, 37:481–494.CrossRefGoogle Scholar
  11. 11.
    Hulsmans HM: The course of radiologic damage during the first six years of rheumatoid arthritis. Arthritis Rheum 2000, 43:1927–1940.PubMedCrossRefGoogle Scholar
  12. 12.
    DeMaria AN: Relative risk of cardiovascular events in patients with rheumatoid arthritis. Am J Cardiol 2002, 89:33D-38D.PubMedCrossRefGoogle Scholar
  13. 13.
    Wijnands MJ: Long-term second-line treatment: a prospective drug survival study. Br J Rheumatol 1992, 31:253–258.PubMedCrossRefGoogle Scholar
  14. 14.
    Kroot EJ: No increased mortality in patients with rheumatoid arthritis: up to 10 years of follow-up from disease onset. Ann Rheum Dis 2000, 59:954–958.PubMedCrossRefGoogle Scholar
  15. 15.
    Linos A: The epidemiology of rheumatoid arthritis in Roches-ter, Minnesota: a study of incidence, prevalence, and mortal-ity. Am J Epidemiol 1980, 111:87–98.PubMedGoogle Scholar
  16. 16.
    Plant MJ: Patterns of radiological progression in early rheu-matoid arthritis: results of an 8 year prospective study. J Rheumatol 1998, 25:417–426.PubMedGoogle Scholar
  17. 17.
    Bukhari M: Time to first occurrence of erosions in inflamma-tory polyarthritis: results from a prospective community-based study. Arthritis Rheum 2001, 44:1248–1253. Observational study on patients with early inflammatory arthritis. Highlights the discrepancies between radiographic progression at a group level and progression at an individual level. Contradicts the view of linear progression in the individual patient.PubMedCrossRefGoogle Scholar
  18. 18.
    Boers M: Randomized comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sul-phasalazine alone in early rheumatoid arthritis. Lancet 1997, 350:309–318.PubMedCrossRefGoogle Scholar
  19. 19.
    Landewé RB: COBRA combination therapy in patients with early rheumatoid arthritis: long-term structural benefits of a brief intervention. Arthritis Rheum 2002, 46:347–356.PubMedCrossRefGoogle Scholar
  20. 20.
    Mottonen T: Comparison of combination therapy with sin-gle- drug therapy in early rheumatoid arthritis: a randomized trial. FIN-RACo trial group. Lancet 1999, 353:1568–1573.PubMedCrossRefGoogle Scholar
  21. 21.
    Lipsky PE: 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, 343:1594–1602.PubMedCrossRefGoogle Scholar
  22. 22.
    Bathon JM: A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med 2000, 343:1586–1593.PubMedCrossRefGoogle Scholar
  23. 23.
    Sokka T, Pincus T: Eligibility of patients in routine care for major clinical trials of anti-tumor necrosis factor alpha agents in rheumatoid arthritis. Arthritis Rheum 2003, 48:313–318. Important observation regarding the external validity of landmark clinical trials. Only a minority of patients in common clinical practice would have met the in- and exclusion criteria of trials with tumor necrosis factor-blocking drugs.PubMedCrossRefGoogle Scholar
  24. 24.
    Bukhari MA: Influence of disease-modifying therapy on radiographic outcome in inflammatory polyarthritis at five years: results from a large observational inception study. Arthritis Rheum 2003, 48:46–53. Observational study on patients with early arthritis, of whom the majority did not fulfil the American College of Rheumatology criteria for RA at baseline. The authors use unprecedented methodology to prove that an early DMARD start retards radiographic progression bet-ter than a delayed DMARD start.PubMedCrossRefGoogle Scholar
  25. 25.
    Lard LR: Early versus delayed treatment in patients with recent-onset rheumatoid arthritis: comparison of two cohorts who received different treatment strategies. Am J Med 2001, 111:446–451. One of the very few clinical trials demonstrating the efficacy of early DMARD treatment.PubMedCrossRefGoogle Scholar
  26. 26.
    Huizinga TW: Criteria for early rheumatoid arthritis: from Bayes’ law revisited to new thoughts on pathogenesis. Arthri-tis Rheum 2002, 46:1155–1159.CrossRefGoogle Scholar

Copyright information

© Current Science Inc 2003

Authors and Affiliations

  • Robert B. M. Landewé
    • 1
  • Désirée M. F. M. van der Heijde
  1. 1.Department of Internal Medicine and RheumatologyUniversity Hospi-tal MaastrichtAZ, MaastrichtThe Netherlands

Personalised recommendations