Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Science and Society
  • Published:

The changing face of rheumatoid arthritis: sustained remission for all?

Nature Reviews Immunology volume 10, pages 605–611 (2010)Cite this article

Subjects

Abstract

Earlier diagnosis and treatment, plus biological therapies, have transformed the outlook for many patients with rheumatoid arthritis. In the future, new biomarkers for diagnosis, prognosis and therapeutic response will further improve outcomes. Additionally, preclinical diagnosis and tolerogenic therapies could provide sustained remission for some individuals, although ethical and societal challenges must also be addressed before rheumatoid arthritis becomes 'yesterday's disease'.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: The pathology of rheumatoid arthritis.
Figure 2: The aetiology of rheumatoid arthritis and timelines of disease onset.
Figure 3: The future pathway for patients with rheumatoid arthritis.

References

  1. The National Audit Office. Sevices for people with rheumatoid arthritis [online] (2009).

  2. Strand, V., Kimberly, R. & Isaacs, J. D. Biologic therapies in rheumatology: lessons learned, future directions. Nature Rev. Drug Discov. 6, 75–92 (2007).

    Article  CAS  Google Scholar 

  3. Cooles, F. A. H. & Isaacs, J. D. Treating to re-establish tolerance in inflammatory arthritis — lessons from other diseases. Best Pract. Res. Clin. Rheumatol. (in the press).

  4. Pratt, A. G., Isaacs, J. D. & Mattey, D. L. Current concepts in the pathogenesis of early rheumatoid arthritis. Best Pract. Res. Clin. Rheumatol 23, 37–48 (2009).

    Article  CAS  Google Scholar 

  5. Chang, S. K., Gu, Z. & Brenner, M. B. Fibroblast-like synoviocytes in inflammatory arthritis pathology: the emerging role of cadherin-11. Immunol. Rev. 233, 256–266 (2010).

    Article  CAS  Google Scholar 

  6. Walsh, N. C. & Gravallese, E. M. Bone remodeling in rheumatic disease: a question of balance. Immunol. Rev. 233, 301–312 (2010).

    Article  CAS  Google Scholar 

  7. Gabriel, S. E. Cardiovascular morbidity and mortality in rheumatoid arthritis. Am. J. Med. 121, S9–S14 (2008).

    Article  Google Scholar 

  8. The National Institute for Healthcare and Clinical Excellence. Rheumatoid arthritis [online] (2009).

  9. Klareskog, L., Catrina, A. I. & Paget, S. Rheumatoid arthritis. Lancet 373, 659–72 (2009).

    Article  CAS  Google Scholar 

  10. Pruijn, G. J., Wiik, A. & van Venrooij, W. J. The use of citrullinated peptides and proteins for the diagnosis of rheumatoid arthritis. Arthritis Res. Ther. 12, 203 (2010).

    Article  Google Scholar 

  11. Hoes, J. N., Jacobs, J. W., Verstappen, S. M., Bijlsma, J. W. & Van der Heijden, G. J. Adverse events of low- to medium-dose oral glucocorticoids in inflammatory diseases: a meta-analysis. Ann. Rheum. Dis. 68, 1833–1838 (2009).

    Article  CAS  Google Scholar 

  12. Fries, J. F. Current treatment paradigms in rheumatoid arthritis. Rheumatology (Oxford) 39, S30–S35 (2000).

    Article  Google Scholar 

  13. Mottonen, T. et al. Comparison of combination therapy with single-drug therapy in early rheumatoid arthritis: a randomised trial. FIN-RACo trial group. Lancet 353, 1568–1573 (1999).

    Article  CAS  Google Scholar 

  14. Landewe, R. B. et al. COBRA combination therapy in patients with early rheumatoid arthritis: long-term structural benefits of a brief intervention. Arthritis Rheum. 46, 347–356 (2002).

    Article  CAS  Google Scholar 

  15. Rantalaiho, V. et al. The good initial response to therapy with a combination of traditional disease-modifying antirheumatic drugs is sustained over time: the eleven-year results of the Finnish rheumatoid arthritis combination therapy trial. Arthritis Rheum. 60, 1222–1231 (2009).

    Article  Google Scholar 

  16. van der Heijde, D. M., van ' t Hof, M., van Riel, P. L. & van de Putte, L. B. Development of a disease activity score based on judgment in clinical practice by rheumatologists. J. Rheumatol. 20, 579–581 (1993).

    CAS  PubMed  Google Scholar 

  17. Grigor, C. et al. Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a single-blind randomised controlled trial. Lancet 364, 263–269 (2004).

    Article  Google Scholar 

  18. Goekoop-Ruiterman, Y. P. et al. Comparison of treatment strategies in early rheumatoid arthritis: a randomized trial. Ann. Intern. Med. 146, 406–415 (2007).

    Article  Google Scholar 

  19. van Vollenhoven, R. F. Treatment of rheumatoid arthritis: state of the art 2009. Nature Rev. Rheumatol. 5, 531–541 (2009).

    Article  CAS  Google Scholar 

  20. Emery, P. et al. Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial. Lancet 372, 375–382 (2008).

    Article  CAS  Google Scholar 

  21. van der Kooij, S. M. et al. Limited efficacy of conventional DMARDs after initial methotrexate failure in patients with recent onset rheumatoid arthritis treated according to the disease activity score. Ann. Rheum. Dis. 66, 1356–1362 (2007).

    Article  CAS  Google Scholar 

  22. van Vollenhoven, R. F. et al. Addition of infliximab compared with addition of sulfasalazine and hydroxychloroquine to methotrexate in patients with early rheumatoid arthritis (Swefot trial): 1-year results of a randomised trial. Lancet 374, 459–466 (2009).

    Article  CAS  Google Scholar 

  23. Smolen, J. S., Aletaha, D., Grisar, J. C., Stamm, T. A. & Sharp, J. T. Estimation of a numerical value for joint damage-related physical disability in rheumatoid arthritis clinical trials. Ann. Rheum. Dis. 69, 1058–1064 (2009).

    Article  Google Scholar 

  24. Aletaha, D. et al. Rheumatoid arthritis joint progression in sustained remission is determined by disease activity levels preceding the period of radiographic assessment. Arthritis Rheum. 60, 1242–1249 (2009).

    Article  CAS  Google Scholar 

  25. Quinn, M. et al. Very early treatment with infliximab in addition to methotrexate in early, poor-prognosis rheumatoid arthritis reduces magnetic resonance imaging evidence of synovitis and damage, with sustained benefit after infliximab withdrawal: results from a twelve-month randomised, double-blind, placebo-controlled trial. Arthritis Rheum. 52, 27–35 (2005).

    Article  CAS  Google Scholar 

  26. da Silva, E., Doran, M. F., Crowson, C. S., O'Fallon, W. M. & Matteson, E. L. Declining use of orthopedic surgery in patients with rheumatoid arthritis? Results of a long-term, population-based assessment. Arthritis Rheum. 49, 216–220 (2003).

    Article  Google Scholar 

  27. van den Hout, W. B. et al. Cost-utility analysis of treatment strategies in patients with recent-onset rheumatoid arthritis. Arthritis Rheum. 61, 291–299 (2009).

    Article  Google Scholar 

  28. van der Kooij, S. M. et al. Drug-free remission, functioning and radiographic damage after 4 years of response-driven treatment in patients with recent-onset rheumatoid arthritis. Ann. Rheum. Dis. 68, 914–921 (2009).

    Article  CAS  Google Scholar 

  29. van Dongen, H. et al. Efficacy of methotrexate treatment in patients with probable rheumatoid arthritis: a double-blind, randomized, placebo-controlled trial. Arthritis Rheum. 56, 1424–1432 (2007).

    Article  CAS  Google Scholar 

  30. Emery, P. et al. Impact of T-cell costimulation modulation in patients with undifferentiated inflammatory arthritis or very early rheumatoid arthritis: a clinical and imaging study of abatacept (the ADJUST trial). Ann. Rheum. Dis. 69, 510–516 (2010).

    Article  CAS  Google Scholar 

  31. Keymeulen, B. et al. Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes. New Engl. J. Med. 352, 2598–2608 (2005).

    Article  CAS  Google Scholar 

  32. Isaacs, J. D. T cell immunomodulation-the Holy Grail of therapeutic tolerance. Curr. Opin. Pharmacol. 7, 418–425 (2007).

    Article  CAS  Google Scholar 

  33. Feldman, D. E. et al. Delay in consultation with specialists for persons with suspected new-onset rheumatoid arthritis: a population-based study. Arthritis Rheum. 57, 1419–1425 (2007).

    Article  Google Scholar 

  34. Kumar, K. et al. Delay in presentation to primary care physicians is the main reason why patients with rheumatoid arthritis are seen late by rheumatologists. Rheumatology (Oxford) 46, 1438–1440 (2007).

    Article  CAS  Google Scholar 

  35. Nielen, M. M. et al. Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors. Arthritis Rheum. 50, 380–386 (2004).

    Article  Google Scholar 

  36. Nielen, M. M. et al. Increased levels of C-reactive protein in serum from blood donors before the onset of rheumatoid arthritis. Arthritis Rheum. 50, 2423–2427 (2004).

    Article  CAS  Google Scholar 

  37. Jorgensen, K. T. et al. Cytokines, autoantibodies and viral antibodies in premorbid and postdiagnostic sera from patients with rheumatoid arthritis: case-control study nested in a cohort of Norwegian blood donors. Ann. Rheum. Dis. 67, 860–866 (2008).

    Article  CAS  Google Scholar 

  38. Karlson, E. W. et al. Biomarkers of inflammation and development of rheumatoid arthritis in women from two prospective cohort studies. Arthritis Rheum. 60, 641–652 (2009).

    Article  CAS  Google Scholar 

  39. Kokkonen, H. et al. Up-regulation of cytokines and chemokines predates the onset of rheumatoid arthritis. Arthritis Rheum. 62, 383–391 (2010).

    CAS  PubMed  Google Scholar 

  40. Kraan, M. C. et al. Asymptomatic synovitis precedes clinically manifest arthritis. Arthritis Rheum. 41, 1481–1488 (1998).

    Article  CAS  Google Scholar 

  41. Oliver, J. E. & Silman, A. J. What epidemiology has told us about risk factors and aetiopathogenesis in rheumatic diseases. Arthritis Res. Ther. 11, 223 (2009).

    Article  Google Scholar 

  42. Bos, W. H., Dijkmans, B. A., Boers, M., van de Stadt, R. J. & van Schaardenburg, D. Effect of dexamethasone on autoantibody levels and arthritis development in patients with arthralgia: a randomised trial. Ann. Rheum. Dis. 69, 571–574 (2010).

    Article  CAS  Google Scholar 

  43. Landewé, R. B. et al. Intranasal administration of recombinant human cartilage glycoprotein-39 as a treatment for rheumatoid arthritis: a Phase II, multicenter, double-blind, randomized, placebo-controlled, parallel group dose-finding trial. Ann. Rheum. Dis. 23 Sep 2009 (doi:10.1136/ard.2009.117234).

    Article  Google Scholar 

  44. Bos, W. H. et al. Arthritis development in patients with arthralgia is strongly associated with anti-citrullinated protein antibody status: a prospective cohort study. Ann. Rheum. Dis. 69, 490–494 (2010).

    Article  CAS  Google Scholar 

  45. Bykerk, V. P. & Hazes, J. M. When does rheumatoid arthritis start and can it be stopped before it does? Ann. Rheum. Dis. 69, 473–475 (2010).

    Article  Google Scholar 

  46. Wakefield, R. J. et al. Should oligoarthritis be reclassified? Ultrasound reveals a high prevalence of subclinical disease. Ann. Rheum. Dis. 63, 382–385 (2004).

    Article  CAS  Google Scholar 

  47. Sheane, B. J., Beddy, P., O'Connor, M., Miller, S. & Cunnane, G. Targeted ultrasound of the fifth metatarsophalangeal joint in an early inflammatory arthritis cohort. Arthritis Rheum. 61, 1004–1008 (2009).

    Article  Google Scholar 

  48. Tamai, M. et al. A prediction rule for disease outcome in patients with undifferentiated arthritis using magnetic resonance imaging of the wrists and finger joints and serologic autoantibodies. Arthritis Rheum. 61, 772–778 (2009).

    Article  CAS  Google Scholar 

  49. Haavardsholm, E. A., Boyesen, P., Ostergaard, M., Schildvold, A. & Kvien, T. K. Magnetic resonance imaging findings in 84 patients with early rheumatoid arthritis: bone marrow oedema predicts erosive progression. Ann. Rheum. Dis. 67, 794–800 (2008).

    Article  CAS  Google Scholar 

  50. Hetland, M. L. et al. MRI bone oedema is the strongest predictor of subsequent radiographic progression in early rheumatoid arthritis. Results from a 2-year randomised controlled trial (CIMESTRA). Ann. Rheum. Dis. 68, 384–390 (2009).

    Article  CAS  Google Scholar 

  51. ten Wolde, S. et al. Randomised placebo-controlled study of stopping second-line drugs in rheumatoid arthritis. Lancet 347, 347–352 (1996).

    Article  CAS  Google Scholar 

  52. Burgoyne, C. H. et al. Abnormal T cell differentiation persists in patients with rheumatoid arthritis in clinical remission and predicts relapse. Ann. Rheum. Dis. 67, 750–757 (2008).

    Article  CAS  Google Scholar 

  53. Verstappen, S. M. et al. The beneficial effects of a 3 week course of intramuscular glucocorticoid injections in patients with very early inflammatory polyarthritis: Results of the STIVEA trial. Ann. Rheum. Dis. 69, 503–509 (2009).

    Article  Google Scholar 

  54. Machold, K. P. et al. The Stop Arthritis Very Early (SAVE) trial, an international multicentre, randomised, double-blind, placebo-controlled trial on glucocorticoids in very early arthritis. Ann. Rheum. Dis. 69, 495–502 (2010).

    Article  CAS  Google Scholar 

  55. Emery, P., Bradley, H., Arthur, V., Tunn, E. & Waring, R. Genetic factors influencing the outcome of early arthritis--the role of sulphoxidation status. Br. J. Rheumatol. 31, 449–451 (1992).

    Article  CAS  Google Scholar 

  56. Barton, A. & Worthington, J. Genetic susceptibility to rheumatoid arthritis: an emerging picture. Arthritis Rheum. 61, 1441–1446 (2009).

    Article  CAS  Google Scholar 

  57. Miossec, P., Korn, T. & Kuchroo, V. K. Interleukin-17 and type 17 helper T cells. N. Engl. J. Med. 361, 888–898 (2009).

    Article  CAS  Google Scholar 

  58. Ehrenstein, M. et al. Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti-TNF α therapy. J. Exp. Med. 200, 277–285 (2004).

    Article  CAS  Google Scholar 

  59. Hamilton, J. A. & Tak, P. P. The dynamics of macrophage lineage populations in inflammatory and autoimmune diseases. Arthritis Rheum. 60, 1210–1221 (2009).

    Article  Google Scholar 

  60. Manzo, A., Bombardieri, M., Humby, F. & Pitzalis, C. Secondary and ectopic lymphoid tissue responses in rheumatoid arthritis: from inflammation to autoimmunity and tissue damage/remodeling. Immunol. Rev. 233, 267–285.

  61. Aupperle, K. R. et al. Regulation of synoviocyte proliferation, apoptosis, and invasion by the p53 tumor suppressor gene. Am. J. Pathol. 152, 1091–1098 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Takayanagi, H. Osteoimmunology and the effects of the immune system on bone. Nature Rev. Rheumatol. 5, 667–676 (2009).

    Article  CAS  Google Scholar 

  63. Kallberg, H. et al. Gene-gene and gene-environment interactions involving HLA-DRB1, PTPN22, and smoking in two subsets of rheumatoid arthritis. Am. J. Hum. Genet. 80, 867–875 (2007).

    Article  Google Scholar 

  64. Kallberg, H. et al. Alcohol consumption is associated with decreased risk of rheumatoid arthritis: results from two Scandinavian case-control studies. Ann. Rheum. Dis. 68, 222–227 (2009).

    Article  CAS  Google Scholar 

  65. Isaacs, J. D. et al. Autoantibody-positive rheumatoid arthritis (RA) patients (pts) have enhanced clinical response to rituximab (RTX) when compared with seronegative patients. Ann. Rheum. Dis. 68 (Suppl. 3), 442 (2009).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. John D. Isaacs is at the Institute of Cellular Medicine, Musculoskeletal Research Group, Newcastle University Medical School, Framlington Place, Newcastle-upon-Tyne NE2 4HH, UK. j.d.isaacs@ncl.ac.uk,

    John D. Isaacs

Authors
  1. John D. Isaacs
    View author publications

    You can also search for this author in PubMed Google Scholar

Ethics declarations

Competing interests

J.D.I. is named on European and US patents relating to the use of non-activating CD3-specific monoclonal antibody for the treatment of inflammatory arthritis.

Related links

Related links

FURTHER INFORMATION

John D. Isaacs's homepage

Rights and permissions

Reprints and permissions

About this article

Cite this article

Isaacs, J. The changing face of rheumatoid arthritis: sustained remission for all?. Nat Rev Immunol 10, 605–611 (2010). https://doi.org/10.1038/nri2804

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nri2804

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research