Drugs

, Volume 66, Issue 10, pp 1319–1337 | Cite as

Early Rheumatoid Arthritis

Pitfalls in Diagnosis and Review of Recent Clinical Trials
Review Article

Abstract

The treatment of rheumatoid arthritis (RA) has changed dramatically in the past decade as advancements in the understanding of the pathobiology of the disease have led to novel therapeutic agents. The recognition that early diagnosis and treatment leads to improvements in morbidity and mortality has altered the therapeutic strategy such that early therapy is now considered the standard of care.

This review focuses on the challenges in making the diagnosis of early RA, including a broad differential diagnosis for inflammatory polyarthritis, poor performance of the standard classification criteria, difficulty in clinical assessment of synovitis, absence of absolute laboratory tests, inability of conventional radiography to detect bony changes early, and barriers to rheumatology care. Additionally, the pathogenesis of RA is highlighted, with particular emphasis on cytokine biology as it relates to therapeutic regimens. Relevant clinical trials in early RA are reviewed and discussed, including trials of combination disease-modifying antirheumatic drugs and biological therapy. The role of induction therapy as a novel therapeutic approach is highlighted. The search for predictors of response is reviewed and the external validity of the trials is analysed. Finally, the trials in early RA therapy suggest that swift intervention with combinations of medications is required for patients with severe RA. However, further research is needed to determine which regimen is appropriate for the individual patient with RA.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Pincus T, Callahan LF, Sale WG, et al. Severe functional declines, work disability, and increased mortality in seventy-five rheumatoid arthritis patients studied over nine years. Arthritis Rheum 1984; 27: 864–72PubMedGoogle Scholar
  2. 2.
    Egsmose C, Lund B, Borg G, et al. Patients with rheumatoid arthritis benefit from early second-line therapy: 5-year follow-up of a prospective double-blind placebo-controlled study. J Rheumatol 1995; 22: 2208–13PubMedGoogle Scholar
  3. 3.
    Lard LR, Visser H, Speyer I, 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: 446–51PubMedGoogle Scholar
  4. 4.
    Tsakonas E, Fitzgerald AA, Fitzcharles MA, et al. Consequences of delayed therapy with second-line agents in rheumatoid arthritis: a 3 year follow-up on the Hydroxychloroquine in Early Rheumatoid Arthritis (HERA) study. J Rheumatol 2000; 27: 623–9PubMedGoogle Scholar
  5. 5.
    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: 699–707PubMedGoogle Scholar
  6. 6.
    Boers M, Verhoeven AC, Markusse HM, et al. Randomized comparison of combined step-down prednisolone, methotrexate and suphasalazine with sulphasalazine alone in early rheumatoid arthritis [published erratum appears in Lancet 1998; 351: 220]. Lancet 1997; 350: 309–18PubMedGoogle Scholar
  7. 7.
    Calguneri M, Pay S, Caliskaner Z, et al. Combination therapy versus monotherapy for the treatment of patients with rheumatoid arthritis. Clin Exp Rheumatol 1999; 17: 699–704PubMedGoogle Scholar
  8. 8.
    Mottonen T, Hannonen P, Leirisalo-Repo M, et al. Comparison of combination therapy with single-drug therapy in early rheumatoid arthritis: a randomized trial. FIN-RACo trial group. Lancet 1999; 353: 1568–73Google Scholar
  9. 9.
    O'Dell JR, Haire CE, Erikson N, et al. Treatment of rheumatoid arthritis with methotrexate alone, sulfasalazine and hydroxychloroquine, or a combination of all three medications. N Engl J Med 1996; 334: 1287–91PubMedGoogle Scholar
  10. 10.
    O'Dell JR, Leff R, Paulsen G. Treatment of rheumatoid arthritis with methotrexate and hydroxychloroquine, methotrexate and sulfasalazine or a combination of three medications: results of a two-year, randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2002; 46: 1164–70PubMedGoogle Scholar
  11. 11.
    Bathon JM, Martin RW, Fleischmann RM, et al. A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis [published errata appear in N Engl J Med 2001; 344: 76; N Engl J Med 2001; 344: 240]. N Engl J Med 2000; 343: 1586–93PubMedGoogle Scholar
  12. 12.
    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: 1532–7PubMedGoogle Scholar
  13. 13.
    Tugwell P, Oritiz Z. Rheumatoid arthritis: emerging evidence for the benefits of early and aggressive therapy. Dis Manage Health Outcomes 1997; 3: 141–53Google Scholar
  14. 14.
    van der Heide DM. Joint erosions and patients with early rheumatoid arthritis. Br J Rheumatol. 1995; 34 Suppl. 2: 74–8Google Scholar
  15. 15.
    Symmons DP, Jones MA, Scott DL, et al. Long-term mortality outcomes in patients with rheumatoid arthritis: early presenters continue to do well. J Rheumatol 1998; 25: 1072–7PubMedGoogle Scholar
  16. 16.
    Arnett FC, Edworthy SM, Bloch DA, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988; 31: 315–24PubMedGoogle Scholar
  17. 17.
    Arendt FC, Edworthy SM, Bloch DA, et al. The American Rheumatism Association 1987 revised criteria for the classification of arthritis. Arthritis Rheum 1988; 31: 315–324Google Scholar
  18. 18.
    Aletaha D, Breedveld FC, Smolen JS. The need for new classification criteria for rheumatoid arthritis. Arthritis Rheum 2005; 52: 3333–6PubMedGoogle Scholar
  19. 19.
    Harrison BJ, Symmons DP, Barrett EM, et al. The performance of the 1987 ARA classification criteria for rheumatoid arthritis in a population based cohort of patients with early inflammatory polyarthritis. J Rheumatol 1998; 25: 2324–30PubMedGoogle Scholar
  20. 20.
    Visser H, le Cessie S, Vos K, et al. How to diagnose rheumatoid arthritis early: a prediction model for persistent (erosive) arthritis. Arthritis Rheum 2002; 46: 357–65PubMedGoogle Scholar
  21. 21.
    Grassi W. Clinical evaluation versus ultrasonography: who is the winner? J Rheumatol 2003; 30: 908–9PubMedGoogle Scholar
  22. 22.
    Schumacher HR, Pessler F, Chen LX. Diagnosing early rheumatoid arthritis (RA): what are the problems and opportunities? Clin Exp Rheumatol 2003; 21 (5 Suppl. 31): S15–S9PubMedGoogle Scholar
  23. 23.
    Ostergaard M, Szkudlarek M. Imaging in rheumatoid arthritis: why MRI and ultrasonography can no longer be ignored. Scand J Rheumatol 2003; 32: 63–73PubMedGoogle Scholar
  24. 24.
    Szkudlarek M, Narvestad E, Klarlund M, et al. Ultrasonography of the metatarsophalangeal joints in rheumatoid arthritis: comparison with magnetic resonance imaging, conventional radiography, and clinical examination. Arthritis Rheum 2004; 50: 2103–12PubMedGoogle Scholar
  25. 25.
    Forslind K, Larsson EM, Eberhardt K, et al. Magnetic resonance imaging of the knee: a tool for prediction of joint damage in early rheumatoid arthritis? Scand J Rheumatol 2004; 33: 154–61PubMedGoogle Scholar
  26. 26.
    Hoving JL, Buchbinder R, Hall S, et al. A comparison of magnetic resonance imaging, sonography, and radiography of the hand in patients with early rheumatoid arthritis. J Rheumatol 2004; 31: 663–75PubMedGoogle Scholar
  27. 27.
    Wakefield RJ, Karim Z, Conaghan PG, et al. Sonography is more sensitive than clinical examination at detecting synovitis in the metatarsophalangeal joints than clinical examination [abstract]. Arthritis Rheum 1999; 42: S352Google Scholar
  28. 28.
    Keen HI, Emery P. How should we manage early rheumatoid arthritis? From imaging to intervention. Curr Opin Rheumatol 2005; 17: 280–5PubMedGoogle Scholar
  29. 29.
    Strunk J, Lange U. Three-dimensional power Doppler sonographic visualization of synovial angiogenesis in rheumatoid arthritis. J Rheumatol 2004; 31: 1004–6PubMedGoogle Scholar
  30. 30.
    Wakefield RJ, Kong KO, Conaghan PG, et al. The role of ultrasonography and magnetic resonance imaging in early rheumatoid arthritis. Clin Exp Rheumatol 2003; 21: S42–S9PubMedGoogle Scholar
  31. 31.
    Combe B, Dougados M, Goupille P, et al. Prognostic factors for radiographic damage in early rheumatoid arthritis: a multiparameter prospective study. Arthritis Rheum 2001; 44: 1736–43PubMedGoogle Scholar
  32. 32.
    Masi AT, Maldonado-Cocco JA, Kaplan SB, et al. Prospective study of the early course of rheumatoid arthritis in young adults: comparison of patients with and without rheumatoid factor positivity at entry and identification of variables correlating with outcome. Semin Arthritis Rheum 1976; 4: 299–326PubMedGoogle Scholar
  33. 33.
    Westedt ML, Herbrink P, Molenaar JL, et al. Rheumatoid factors in rheumatoid arthritis and vasculitis. Rheumatol Int 1985; 5: 209–14PubMedGoogle Scholar
  34. 34.
    Berglin E, Padyukov L, Sundin U, et al. A combination of autoantibodies to cyclic citrullinated peptide (CCP) and HLA-DRB1 locus antigens is strongly associated with future onset of rheumatoid arthritis. Arthritis Res Ther 2004; 6: 303–8Google Scholar
  35. 35.
    Goldbach-Mansky R, Lee J, McCoy A, et al. Rheumatoid arthritis associated autoantibodies in patients with synovitis of recent onset. Arthritis Res 2000; 2: 236–43PubMedGoogle Scholar
  36. 36.
    Choy EH, Panayi GS. Cytokine Pathways and joint inflammation in rheumatoid arthritis. N Engl J Med 2001; 344: 907–16PubMedGoogle Scholar
  37. 37.
    Gonzalez-Gay MA, Garcia-Porrua C, Hajeer AH. Influence of human leukocyte antigen-DRB1 on the susceptibility and severity of rheumatoid arthritis. Semin Arthritis Rheum 2002; 31: 355–60PubMedGoogle Scholar
  38. 38.
    Gregersen PK, Silver J, Winchester RJ. The shared epitope hypothesis: an approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum 1987; 30: 1205–313PubMedGoogle Scholar
  39. 39.
    Shingu M, Nagai Y, Isayama T, et al. The effects of cytokines on metalloproteinase inhibitors (TIMP) and collagenase production by human cohondrocytes and TMP production by synovial cells and endothelial cells. Clin Exp Immunol 1993; 94: 145–9PubMedGoogle Scholar
  40. 40.
    Girasole G, Passeri G, Jilka RL, et al. Interleukin-11: a new cytokine critical for osteoclast development. J Clin Invest 1994; 93: 1516–24PubMedGoogle Scholar
  41. 41.
    Cannella A, O'Dell J. Use of combination therapy for rheumatoid arthritis. J Musculoskeletal Med 2003; 20: 162–70Google Scholar
  42. 42.
    Harris ED Jr. The rationale for combination therapy of rheumatoid arthritis based on pathophysiology. J Rheumatol 1996; 23 Suppl. 44: 2–4Google Scholar
  43. 43.
    Cannella AC, O'Dell JR. Is there still a role for traditional disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis? Curr Opin Rheumatol 2003; 15: 185–92PubMedGoogle Scholar
  44. 44.
    Felson DT, Anderson JJ, Meenan RF. The comparative efficacy and toxicity of second-line drugs in rheumatoid arthritis: results of two meta-analyses. Arthritis Rheum 1990; 33: 1449–61PubMedGoogle Scholar
  45. 45.
    Pincus T, Marcum SB, Callahan LF. Long-term drug therapy for rheumatoid art 1hritis in seven rheumatology private practices: second line drugs and prednisone. J Rheumatol 1992; 19: 1885–94PubMedGoogle Scholar
  46. 46.
    Wolfe F, Hawley DJ, Cathey MA. Termination of a slow acting antirheumatic therapy in rheumatoid arthritis: a 14 year prospective evaluation of 1017 consecutive starts. J Rheumatol 1990; 17: 994–1002PubMedGoogle Scholar
  47. 47.
    Mikuls T, O'Dell JR. The treatment of rheumatoid arthritis: current trends in therapy [abstract]. Arthritis Rheum 1999; 42: S79Google Scholar
  48. 48.
    O'Dell JR. Methotrexate use in rheumatoid arthritis. Rheum Dis Clin North Am 1997; 23: 779–96PubMedGoogle Scholar
  49. 49.
    Williams HJ, Willkens RF, Samuelson CO Jr, et al. Comparison of low-dose oral pulse methotrexate and placebo in the treatment of rheumatoid arthritis: a controlled clinical trial. Arthritis Rheum 1985; 28: 721–30PubMedGoogle Scholar
  50. 50.
    Kremer JM. Safety, efficacy and mortality in a long-term cohort of patients with rheumatoid arthritis taking methotrexate: follow-up after mean of 13.3 years. Arthritis Rheum 1997; 40: 984–5PubMedGoogle Scholar
  51. 51.
    Morgan SL, Baggott JE, Vaughn WH, et al. Supplementation with folic acid during methotrexate therapy for rheumatoid arthritis: a double-blind, placebo controlled trial. Ann Intern Med 1994; 121: 833–41PubMedGoogle Scholar
  52. 52.
    Weinblatt M. Methotrexate (MTX) in rheumatoid arthritis (RA): a 5 year multi prospective trial [abstract]. Arthritis Rheum 1993; 36: S79Google Scholar
  53. 53.
    Svartz N. Salazopyrin, a new sulfanilamide preparation. Acta Med Scand 1942; 110: 577Google Scholar
  54. 54.
    Herman K, Leys A, Spileers W. (Hydroxy)-chloroquine retinal toxicity: two case reports and safety guidelines. Bull Soc Belge Ophtalmol 2002; 284: 21–9PubMedGoogle Scholar
  55. 55.
    Smolen JS, Kalden JR, Scott DL, et al. Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheumatoid arthritis: a double-blind randomized, multicenter trial. European Leflunomide Study Group. Lancet 1999; 353: 259–66Google Scholar
  56. 56.
    Strand V, Cohen S, Schiff M, et al. On behalf of the Leflunomide Rheumatoid Arthritis Investigators Group. Treatment of active rheumatoid arthritis with leflunomide compared with placebo and methotrexate. Arch Intern Med 1999; 159: 2542–50Google Scholar
  57. 57.
    O'Dell JR, Blakely KW, Mallek JA, et al. Treatment of early seropositive rheumatoid arthritis: a two-year, double-blind comparison of minocycline and hydroxychloroquine. Arthritis Rheum 2001; 44: 2235–41PubMedGoogle Scholar
  58. 58.
    O'Dell JR, Haire CE, Palmer W, et al. Treatment of early rheumatoid arthritis with minocycline or placebo. Arthritis Rheum 2002; 40: 842–8Google Scholar
  59. 59.
    O'Dell JR, Paulsen G, Haire CE, et al. Treatment of early seropositive rheumatoid arthritis with minocycline: four-year followup of a double-blind, placebo-controlled trial. Arthritis Rheum 1999; 42: 1691–5PubMedGoogle Scholar
  60. 60.
    Kirwan JR. The effect of glucocorticoid on joint destruction in rheumatoid arthritis: the Arthritis and Rheumatism Council Low-Dose Glucocorticoid Study Group. N Engl J Med 1995; 333: 142–6PubMedGoogle Scholar
  61. 61.
    Kwoh CK, Anderson LG, Greene JM, et al. Guidelines for the management of rheumatoid arthritis. Arthritis Rheum 2002; 46: 328–46Google Scholar
  62. 62.
    Simms RW, Kwoh CK, Anderson LG, et al. Guidelines for monitoring drug therapy in rheumatoid arthritis: American College of Rheumatology Ad Hoc Committee on Clinical Guidelines. Arthritis Rheum 1996; 39: 723–31Google Scholar
  63. 63.
    van der Heijde DM, van't Hof M, van Riel PL, et al. Development of a disease activity score based on judgment in clinical practice by rheumatologists. J Rheumatol 1993; 20: 579–81PubMedGoogle Scholar
  64. 64.
    Felson DT, Anderson JJ, Boers M, et al. Preliminary definition of improvement in rheumatoid arthritis. American College of Rheumatology. Arthritis Rheum 1995; 38: 727–35Google Scholar
  65. 65.
    Paulus HE, Egger MJ, Ward JR, et al. Analysis of improvement in individual rheumatoid arthritis patients treated with disease-modifying antirheumatic drugs, based on the findings in patients treated with placebo: the Cooperative Systematic Studies of Rheumatic Diseases Group. Arthritis Rheum 1990; 33: 477–84PubMedGoogle Scholar
  66. 66.
    Scott DL. A simple index to assess disease activity in RA. J Rheumatol 1993; 20: 582–4PubMedGoogle Scholar
  67. 67.
    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: 34–40PubMedGoogle Scholar
  68. 68.
    Tugwell P, Pincus T, Yocum D, et al. Combination therapy with cyclosporine and methotrexate in severe rheumatoid arthritis: the Methotrexate-Cyclosporine Combination Study Group. N Engl J Med 1995; 333: 137–42PubMedGoogle Scholar
  69. 69.
    Dougados M, Combe B, Cantagrel A, et al. Combination therapy in early rheumatoid arthritis: a randomised, controlled, double blind 52 week clinical trial of sulphasalazine and methotrexate compared with the single components. Ann Rheum Dis 1999; 58: 220–5PubMedGoogle Scholar
  70. 70.
    Haagsma CJ, van Riel PL, de Jong AJ, et al. Combination of sulphasalazine and methotrexate versus the single components in early rheumatoid arthritis: a randomized, controlled, double-blind, 52 week clinical trial. Br J Rheumatol 1997; 36: 1082–8PubMedGoogle Scholar
  71. 71.
    Landewe RB, Boers M, Verhoeven AC, et al. COBRA combination therapy in patients with early rheumatoid arthritis: long-term structural benefits of a brief intervention. Arthritis Rheum 2002; 46: 347–56PubMedGoogle Scholar
  72. 72.
    Pinals RS, Masi AT, Larsen RA, et al. Preliminary criteria for clinical remission in rheumatoid arthritis. Arthritis Rheum 1981; 24: 1308–15PubMedGoogle Scholar
  73. 73.
    Neva MH, Kauppi MJ, Kautiainen H, et al. Combination drug therapy retards the development of rheumatoid atlantoaxial subluxations. Arthritis Rheum 2000; 11: 2397–401Google Scholar
  74. 74.
    Elliot J, Maini R, Reldmann M, et al. Randomized double-blind comparison of chimeric monoclonal antibody to tumor necrosis factor alpha (eA2) versus placebo in rheumatoid arthritis. Lancet 1994; 344: 1101–10Google Scholar
  75. 75.
    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: 1594–602PubMedGoogle Scholar
  76. 76.
    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: 1552–63PubMedGoogle Scholar
  77. 77.
    Keystone E, Kavanaugh AF, Sharp J, et al. Adalimumab (D2E7), a fully human anti-tnf-alpha monoclonal antibody inhibits the progression of structural joint damage in patients with active RA despite concomitant methotrexate therapy [abstract]. Arthritis Rheum 2002; 46: S205Google Scholar
  78. 78.
    Keystone E, Weinblatt M, Furst D, et al. The ARMADA trial: A double-blind placebo controlled trial of the fully human anti-TNF monoclonal antibody, adalimumab (D2E7) in patients with active RA on methotrexate (MTX) [abstract no. 965]. Arthritis Rheum 2001; 44: S213Google Scholar
  79. 79.
    Van De Putte LBA, Atkins C, Malaise M, et al. Adalimumab (D2E7) monotherapy in the treatment of patients with rheumatoid arthritis. Arthritis Rheum 2002; 46: S205Google Scholar
  80. 80.
    Moreland LW, Baumgartner SW, Schiff MH, et al. Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein. N Engl J Med 1997; 337: 141–7PubMedGoogle Scholar
  81. 81.
    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: 253–9PubMedGoogle Scholar
  82. 82.
    Keane J. TNF-blocking agents and tuberculosis: new drugs illuminate an old topic. Rheumatology (Oxford) 2005; 44: 714–20Google Scholar
  83. 83.
    Mohan AK, Cote TR, Siegel JN, et al. Infectious complications of biologic treatments of rheumatoid arthritis. Curr Opin Rheumatol 2003; 15: 179–84PubMedGoogle Scholar
  84. 84.
    Favalli EG, Sinigaglia L, Varenna M, et al. Drug-induced lupus following treatment with infliximab in rheumatoid arthritis. Lupus 2002; 11: 753–5PubMedGoogle Scholar
  85. 85.
    Hochberg MC, Lebwohl MG, Plevy SE, et al. The benefit/risk profile of TNF-blocking agents: findings of a consensus panel. Semin Arthritis Rheum 2005; 34: 819–36PubMedGoogle Scholar
  86. 86.
    Klippel JH. Biologic therapy for rheumatoid arthritis [published erratum appears in N Engl J Med 2001; 344:76]. N Engl J Med 2000; 343: 1640–2PubMedGoogle Scholar
  87. 87.
    Shakoor N, Michalska M, Harris CA, et al. Drug-induced systemic lupus erythematosus associated with etanercept therapy. Lancet 2002; 359: 579–80PubMedGoogle Scholar
  88. 88.
    Brown SL, Greene MH, Gershon SK, et al. Tumor necrosis factor antagonist therapy and lymphoma development: twenty-six cases reported to the Food and Drug Administration. Arthritis Rheum 2002; 46: 3151–8PubMedGoogle Scholar
  89. 89.
    Geborek P, Blastrom A, Turreson C, et al. Tumor necrosis factor blockers do not increase overall tumour risk in patients with rheumatoid arthritis, but may be associated with and increased risk of lymphomas. Ann Rheum Dis 2005; 64: 699–703PubMedGoogle Scholar
  90. 90.
    Baecklund E, Elkbom A, Sparen P, et al. Disease activity and risk of lymphoma in patients with rheumatoid arthritis: nested case-control study. BMJ 1998; 317: 180–1PubMedGoogle Scholar
  91. 91.
    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: 1564–70PubMedGoogle Scholar
  92. 92.
    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: 706–20PubMedGoogle Scholar
  93. 93.
    van der Heijde DM, van Leeuwen MA, van Riel PL, et al. Biannual radiographic assessments of hands and feet in the three-year prospective followup of patients with early rheumatoid arthritis. Arthritis Rheum 1991; 35: 26–34Google Scholar
  94. 94.
    Genovese MC, Bathon JM, Martin RW, et al. Etanercept versus methotrexate in patients with early rheumatoid arthritis: two-year radiographic outcomes. Arthritis Rheum 2002; 46: 1443–50PubMedGoogle Scholar
  95. 95.
    Emery P, Seto Y. Role of biologics in early arthritis. Clin Exp Rheumatol 2003; 21 (5 Suppl. 31): S191–4PubMedGoogle Scholar
  96. 96.
    Klareskog L, van der Heijde D, de Jager JP, et al. TEMPO (Trial of Etanercept and Methotrexate with radiographic Patient Outcomes) study investigators. 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: 675–81Google Scholar
  97. 97.
    van der Heide A, Klareskog L, Wajdula J, et al. Halting of radiographic progression in RA patients treated with etanercept and methotrexate: year 2 results from the TEMPO trial [poster]. American College of Rheumatology Annual Meeting; 2004 Oct 16–21; San Antonio (TX)Google Scholar
  98. 98.
    St Clair EW, van der Heijde DM, Smolen JS, et al. Combination of infliximab and methotrexate therapy for early rheumatoid arthritis. Arthritis Rheum 2004; 50: 3432–43Google Scholar
  99. 99.
    van der Heijde DM. Plain x-rays in rheumatoid arthritis: overview of scoring methods, their reliability and applicability. Ballieres Clin Rheumatol 1996; 10: 435–53Google Scholar
  100. 100.
    Breedveld FC, Weisman MH, Kavanaugh AF, et al. A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early aggressive rheumatoid arthritis who had not had previous methotrexate treatment: the PREMIER study. Arthritis Rheum 2006; 54(1): 26–37PubMedGoogle Scholar
  101. 101.
    Pavelka K, Kvien TK, Cohen SB, et al. Failure to inhibit radiographic progression within the first 6 months of therapy leads to worse radiographic outcomes at 2 years. EULAR; 2005 Jun 8–11; ViennaGoogle Scholar
  102. 102.
    Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, et al. Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt Study). Arthritis Rheum 2005; 52: 3381–90PubMedGoogle Scholar
  103. 103.
    Grigor C, Capell H, Stirling A, et al. Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a single-blind randomised controlled clinical trial. Lancet 2004; 364: 263–9PubMedGoogle Scholar
  104. 104.
    O'Dell JR. Treating rheumatoid arthritis early: a window of opportunity? Arthritis Rheum 2002; 46: 283–5PubMedGoogle Scholar
  105. 105.
    Quinn MA, Conaghan PG, O'Connor PJ, 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. Arthritis Rheum 2005; 52: 27–35PubMedGoogle Scholar
  106. 106.
    Gossec L, Dougados M. Combination therapy in early rheumatoid arthritis. Clin Exp Rheumatol 2003; 21 (5 Suppl. 31): S174–8PubMedGoogle Scholar
  107. 107.
    Smolen JS, Aletaha D, Keystone E. Superior efficacy of combination therapy for rheumatoid arthritis: fact or fiction? Arthritis Rheum 2005; 52(10): 2975–83PubMedGoogle Scholar
  108. 108.
    Bukhari M, Lunt M, Harrison BJ, et al. Rheumatoid factor is the major predictor of increasing severity of radiographic erosions in rheumatoid arthritis: results from the Norfolk Arthritis Register Study, a large inception cohort. Arthritis Rheum 2002; 46: 906–12PubMedGoogle Scholar
  109. 109.
    Forslind K, Ahlmen M, Eberhardt K, et al. Prediction of radiological outcome in early rheumatoid arthritis in clinical practice: role of antibodies to citrullinated peptides (anti-CCP). Ann Rheum Dis 2004; 63: 1090–5PubMedGoogle Scholar
  110. 110.
    Teitsson I. IgA rheumatoid factor as predictor of disease activity. Scand J Rheumatol Suppl 1988; 75: 233–7PubMedGoogle Scholar
  111. 111.
    Harrison B, Symmons D. Early inflammatory polyarthritis: results from the Norfolk Arthritis Register with a review of the literature: II. Outcome at three years. Rheumatology 2000; 39: 939–49Google Scholar
  112. 112.
    O'Dell JR, Nepom BS, Haire C, et al. HLA-DRB1 typing in rheumatoid arthritis: predicting response to specific treatments. Ann Rheum Dis 1998; 57: 209–13PubMedGoogle Scholar
  113. 113.
    Lard LR, Boers M, Verhoeven A, et al. Early and aggressive treatment of rheumatoid arthritis patients affects the association of HLA class II antigens with progression of joint damage. Arthritis Rheum 2002; 46: 889–905Google Scholar
  114. 114.
    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: 313–8PubMedGoogle Scholar
  115. 115.
    Yazici Y, Erkan D. Eligibility of rheumatoid arthritis patients seen in clinical practice for rheumatoid arthritis clinical trials: comment on the article by Sokka and Pincus. Arthritis Rheum 2003; 48: 3611–3PubMedGoogle Scholar

Copyright information

© Adis Data Information BV 2006

Authors and Affiliations

  1. 1.983025 University of Nebraska Medical CenterOmahaUSA

Personalised recommendations