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General principles of management of rheumatoid arthritis in adults

Authors
Larry W Moreland, MD
Amy Cannella, MD, MS, RhMSUS
Section Editor
James R O'Dell, MD
Deputy Editor
Paul L Romain, MD

INTRODUCTION

The treatment of rheumatoid arthritis (RA) is directed toward the control of synovitis and the prevention of joint injury. The choice of therapies depends upon several factors, including the severity of disease activity when therapy is initiated and the response of the patient to prior therapeutic interventions.

Common principles that guide management strategies and the choice of agents have been derived from an increased understanding of the disease and evidence from clinical trials and other studies. These strategies include approaches directed at achieving remission or low disease activity by more rapid and sustained control of inflammation by the institution of disease-modifying antirheumatic drug (DMARD) therapy early in the disease course.

The general principles and treatment strategies that should be applied to the management of RA are reviewed here. The initial therapy of RA and the treatment of patients resistant to initial DMARDs are discussed in greater detail elsewhere. (See "Nonpharmacologic therapies and preventive measures for patients with rheumatoid arthritis" and "Alternatives to methotrexate for the initial treatment of rheumatoid arthritis in adults" and "Initial treatment of rheumatoid arthritis in adults" and "Treatment of rheumatoid arthritis in adults resistant to initial nonbiologic DMARD therapy" and "Treatment of rheumatoid arthritis in adults resistant to initial biologic DMARD therapy".)

GENERAL PRINCIPLES

Our overall approach to the treatment of patients with rheumatoid arthritis (RA) depends upon the timely and judicious use of several types of therapeutic interventions. The appropriate use of these therapies is based upon an understanding of a group of general principles that have been widely accepted by major working groups and by professional organizations of rheumatologists [1-5]. (See 'Recommendations by major groups' below.)

These principles include:

                                   

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Literature review current through: Nov 2016. | This topic last updated: Fri Jul 22 00:00:00 GMT+00:00 2016.
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References
Top
  1. Singh JA, Furst DE, Bharat A, et al. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken) 2012; 64:625.
  2. Smolen JS, Aletaha D, Bijlsma JW, et al. Treating rheumatoid arthritis to target: recommendations of an international task force. Ann Rheum Dis 2010; 69:631.
  3. Smolen JS, Landewé R, Breedveld FC, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann Rheum Dis 2010; 69:964.
  4. Smolen JS, Landewé R, Breedveld FC, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis 2014; 73:492.
  5. Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care Res (Hoboken) 2016; 68:1.
  6. Knevel R, Schoels M, Huizinga TW, et al. Current evidence for a strategic approach to the management of rheumatoid arthritis with disease-modifying antirheumatic drugs: a systematic literature review informing the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis 2010; 69:987.
  7. Schoels M, Knevel R, Aletaha D, et al. Evidence for treating rheumatoid arthritis to target: results of a systematic literature search. Ann Rheum Dis 2010; 69:638.
  8. McInnes IB, O'Dell JR. State-of-the-art: rheumatoid arthritis. Ann Rheum Dis 2010; 69:1898.
  9. Sokka T, Pincus T. Rheumatoid arthritis: strategy more important than agent. Lancet 2009; 374:430.
  10. Klareskog L, Catrina AI, Paget S. Rheumatoid arthritis. Lancet 2009; 373:659.
  11. Scott DL, Wolfe F, Huizinga TW. Rheumatoid arthritis. Lancet 2010; 376:1094.
  12. 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.
  13. Pincus T, Sokka T, Kautiainen H. Patients seen for standard rheumatoid arthritis care have significantly better articular, radiographic, laboratory, and functional status in 2000 than in 1985. Arthritis Rheum 2005; 52:1009.
  14. Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 2010; 62:2569.
  15. Huizinga TW, Pincus T. In the clinic. Rheumatoid arthritis. Ann Intern Med 2010; 153:ITC1.
  16. Ward MM, Leigh JP, Fries JF. Progression of functional disability in patients with rheumatoid arthritis. Associations with rheumatology subspecialty care. Arch Intern Med 1993; 153:2229.
  17. Solomon DH, Bates DW, Panush RS, Katz JN. Costs, outcomes, and patient satisfaction by provider type for patients with rheumatic and musculoskeletal conditions: a critical review of the literature and proposed methodologic standards. Ann Intern Med 1997; 127:52.
  18. Criswell LA, Such CL, Yelin EH. Differences in the use of second-line agents and prednisone for treatment of rheumatoid arthritis by rheumatologists and non-rheumatologists. J Rheumatol 1997; 24:2283.
  19. Rat AC, Henegariu V, Boissier MC. Do primary care physicians have a place in the management of rheumatoid arthritis? Joint Bone Spine 2004; 71:190.
  20. Lacaille D, Anis AH, Guh DP, Esdaile JM. Gaps in care for rheumatoid arthritis: a population study. Arthritis Rheum 2005; 53:241.
  21. van der Linden MP, le Cessie S, Raza K, et al. Long-term impact of delay in assessment of patients with early arthritis. Arthritis Rheum 2010; 62:3537.
  22. Saag KG, Teng GG, Patkar NM, et al. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum 2008; 59:762.
  23. Fleischmann R, Kremer J, Cush J, et al. Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis. N Engl J Med 2012; 367:495.
  24. van Vollenhoven RF, Fleischmann R, Cohen S, et al. Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. N Engl J Med 2012; 367:508.
  25. van der Heijde DM, van Leeuwen MA, van Riel PL, et al. Biannual radiographic assessments of hands and feet in a three-year prospective followup of patients with early rheumatoid arthritis. Arthritis Rheum 1992; 35:26.
  26. 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; 16:585.
  27. Wakefield RJ, Gibbon WW, Conaghan PG, et al. The value of sonography in the detection of bone erosions in patients with rheumatoid arthritis: a comparison with conventional radiography. Arthritis Rheum 2000; 43:2762.
  28. Weidekamm C, Köller M, Weber M, Kainberger F. Diagnostic value of high-resolution B-mode and doppler sonography for imaging of hand and finger joints in rheumatoid arthritis. Arthritis Rheum 2003; 48:325.
  29. McQueen FM. The use of MRI in early RA. Rheumatology (Oxford) 2008; 47:1597.
  30. Anderson JJ, Wells G, Verhoeven AC, Felson DT. Factors predicting response to treatment in rheumatoid arthritis: the importance of disease duration. Arthritis Rheum 2000; 43:22.
  31. 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.
  32. Nell VP, Machold KP, Eberl G, et al. Benefit of very early referral and very early therapy with disease-modifying anti-rheumatic drugs in patients with early rheumatoid arthritis. Rheumatology (Oxford) 2004; 43:906.
  33. Sokka T, Mäkinen H. Drug management of early rheumatoid arthritis - 2008. Best Pract Res Clin Rheumatol 2009; 23:93.
  34. Emery P, Kvien TK, Combe B, et al. Combination etanercept and methotrexate provides better disease control in very early (<=4 months) versus early rheumatoid arthritis (>4 months and <2 years): post hoc analyses from the COMET study. Ann Rheum Dis 2012; 71:989.
  35. Molina E, Del Rincon I, Restrepo JF, et al. Association of socioeconomic status with treatment delays, disease activity, joint damage, and disability in rheumatoid arthritis. Arthritis Care Res (Hoboken) 2015; 67:940.
  36. van Nies JA, Tsonaka R, Gaujoux-Viala C, et al. Evaluating relationships between symptom duration and persistence of rheumatoid arthritis: does a window of opportunity exist? Results on the Leiden early arthritis clinic and ESPOIR cohorts. Ann Rheum Dis 2015; 74:806.
  37. Anderson J, Caplan L, Yazdany J, et al. Rheumatoid arthritis disease activity measures: American College of Rheumatology recommendations for use in clinical practice. Arthritis Care Res (Hoboken) 2012; 64:640.
  38. Pincus T, Swearingen CJ, Bergman MJ, et al. RAPID3 (Routine Assessment of Patient Index Data) on an MDHAQ (Multidimensional Health Assessment Questionnaire): agreement with DAS28 (Disease Activity Score) and CDAI (Clinical Disease Activity Index) activity categories, scored in five versus more than ninety seconds. Arthritis Care Res (Hoboken) 2010; 62:181.
  39. Wolfe F, Michaud K, Pincus T. A composite disease activity scale for clinical practice, observational studies, and clinical trials: the patient activity scale (PAS/PAS-II). J Rheumatol 2005; 32:2410.
  40. American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the management of rheumatoid arthritis: 2002 Update. Arthritis Rheum 2002; 46:328.
  41. Fries JF, Spitz PW, Young DY. The dimensions of health outcomes: the health assessment questionnaire, disability and pain scales. J Rheumatol 1982; 9:789.
  42. Fries JF, Spitz P, Kraines RG, Holman HR. Measurement of patient outcome in arthritis. Arthritis Rheum 1980; 23:137.
  43. McDowell I, Newell C. health: A guide to rating scales and questionnaires, 2nd, Oxford University Press, New York 1996. p.106.
  44. Wolfe F. Which HAQ is best? A comparison of the HAQ, MHAQ and RA-HAQ, a difficult 8 item HAQ (DHAQ), and a rescored 20 item HAQ (HAQ20): analyses in 2,491 rheumatoid arthritis patients following leflunomide initiation. J Rheumatol 2001; 28:982.
  45. Smolen JS, Breedveld FC, Schiff MH, et al. A simplified disease activity index for rheumatoid arthritis for use in clinical practice. Rheumatology (Oxford) 2003; 42:244.
  46. O'Dell JR. Combination DMARD therapy for rheumatoid arthritis: a step closer to the goal. Ann Rheum Dis 1996; 55:781.
  47. 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; 35:1117.
  48. Guidelines for monitoring drug therapy in rheumatoid arthritis. American College of Rheumatology Ad Hoc Committee on Clinical Guidelines. Arthritis Rheum 1996; 39:723.
  49. Khanna D, Ranganath VK, Fitzgerald J, et al. Increased radiographic damage scores at the onset of seropositive rheumatoid arthritis in older patients are associated with osteoarthritis of the hands, but not with more rapid progression of damage. Arthritis Rheum 2005; 52:2284.
  50. Ruta S, Reginato AM, Pineda C, et al. General applications of ultrasound in rheumatology: why we need it in our daily practice. J Clin Rheumatol 2015; 21:133.
  51. 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; 42:1706.
  52. Østergaard M, Møller-Bisgaard S. Optimal use of MRI in clinical trials, clinical care and clinical registries of patients with rheumatoid arthritis. Clin Exp Rheumatol 2014; 32:S.
  53. 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): a randomized, controlled trial. Arthritis Rheum 2005; 52:3381.
  54. Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, et al. Comparison of treatment strategies in early rheumatoid arthritis: a randomized trial. Ann Intern Med 2007; 146:406.
  55. de Vries-Bouwstra JK, Goekoop-Ruiterman YP, Verpoort KN, et al. Progression of joint damage in early rheumatoid arthritis: association with HLA-DRB1, rheumatoid factor, and anti-citrullinated protein antibodies in relation to different treatment strategies. Arthritis Rheum 2008; 58:1293.
  56. Möttönen 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; 353:1568.
  57. Puolakka K, Kautiainen H, Möttönen T, et al. Impact of initial aggressive drug treatment with a combination of disease-modifying antirheumatic drugs on the development of work disability in early rheumatoid arthritis: a five-year randomized followup trial. Arthritis Rheum 2004; 50:55.
  58. Rantalaiho V, Korpela M, Hannonen P, 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 2009; 60:1222.
  59. 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 trial. Lancet 2004; 364:263.
  60. van der Kooij SM, Goekoop-Ruiterman YP, de Vries-Bouwstra JK, 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 2009; 68:914.
  61. Finckh A, Bansback N, Marra CA, et al. Treatment of very early rheumatoid arthritis with symptomatic therapy, disease-modifying antirheumatic drugs, or biologic agents: a cost-effectiveness analysis. Ann Intern Med 2009; 151:612.
  62. Stoffer MA, Schoels MM, Smolen JS, et al. Evidence for treating rheumatoid arthritis to target: results of a systematic literature search update. Ann Rheum Dis 2016; 75:16.
  63. Bathon JM, Cohen SB. The 2008 American College of Rheumatology recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis: where the rubber meets the road. Arthritis Rheum 2008; 59:757.
  64. Smolen JS, Breedveld FC, Burmester GR, et al. Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force. Ann Rheum Dis 2016; 75:3.
  65. Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol 2016; 68:1.
  66. Schipper LG, van Hulst LT, Grol R, et al. Meta-analysis of tight control strategies in rheumatoid arthritis: protocolized treatment has additional value with respect to the clinical outcome. Rheumatology (Oxford) 2010; 49:2154.
  67. Rantalaiho V, Korpela M, Laasonen L, et al. Early combination disease-modifying antirheumatic drug therapy and tight disease control improve long-term radiologic outcome in patients with early rheumatoid arthritis: the 11-year results of the Finnish Rheumatoid Arthritis Combination Therapy trial. Arthritis Res Ther 2010; 12:R122.
  68. Leirisalo-Repo M, Kautiainen H, Laasonen L, et al. Infliximab for 6 months added on combination therapy in early rheumatoid arthritis: 2-year results from an investigator-initiated, randomised, double-blind, placebo-controlled study (the NEO-RACo Study). Ann Rheum Dis 2013; 72:851.
  69. Moreland LW, O'Dell JR, Paulus HE, et al. A randomized comparative effectiveness study of oral triple therapy versus etanercept plus methotrexate in early aggressive rheumatoid arthritis: the treatment of Early Aggressive Rheumatoid Arthritis Trial. Arthritis Rheum 2012; 64:2824.
  70. Pincus T, Castrejón I. Evidence that the strategy is more important than the agent to treat rheumatoid arthritis. Data from clinical trials of combinations of non-biologic DMARDs, with protocol-driven intensification of therapy for tight control or treat-to-target. Bull Hosp Jt Dis (2013) 2013; 71 Suppl 1:S33.
  71. Kirwan JR. The effect of glucocorticoids on joint destruction in rheumatoid arthritis. The Arthritis and Rheumatism Council Low-Dose Glucocorticoid Study Group. N Engl J Med 1995; 333:142.
  72. Kirwan JR, Bijlsma JW, Boers M, Shea BJ. Effects of glucocorticoids on radiological progression in rheumatoid arthritis. Cochrane Database Syst Rev 2007; :CD006356.
  73. Bakker MF, Jacobs JW, Welsing PM, et al. Low-dose prednisone inclusion in a methotrexate-based, tight control strategy for early rheumatoid arthritis: a randomized trial. Ann Intern Med 2012; 156:329.
  74. Hoes JN, Jacobs JW, Verstappen SM, et al. Adverse events of low- to medium-dose oral glucocorticoids in inflammatory diseases: a meta-analysis. Ann Rheum Dis 2009; 68:1833.
  75. Da Silva JA, Jacobs JW, Kirwan JR, et al. Safety of low dose glucocorticoid treatment in rheumatoid arthritis: published evidence and prospective trial data. Ann Rheum Dis 2006; 65:285.
  76. Visser K, Katchamart W, Loza E, et al. Multinational evidence-based recommendations for the use of methotrexate in rheumatic disorders with a focus on rheumatoid arthritis: integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E Initiative. Ann Rheum Dis 2009; 68:1086.
  77. Ariza-Ariza R, Navarro-Sarabia F, Hernández-Cruz B, et al. Dose escalation of the anti-TNF-alpha agents in patients with rheumatoid arthritis. A systematic review. Rheumatology (Oxford) 2007; 46:529.
  78. Rahman MU, Strusberg I, Geusens P, et al. Double-blinded infliximab dose escalation in patients with rheumatoid arthritis. Ann Rheum Dis 2007; 66:1233.
  79. Pavelka K, Jarosová K, Suchý D, et al. Increasing the infliximab dose in rheumatoid arthritis patients: a randomised, double blind study failed to confirm its efficacy. Ann Rheum Dis 2009; 68:1285.
  80. van Vollenhoven RF. How to dose infliximab in rheumatoid arthritis: new data on a serious issue. Ann Rheum Dis 2009; 68:1237.
  81. Johnsen AK, Schiff MH, Mease PJ, et al. Comparison of 2 doses of etanercept (50 vs 100 mg) in active rheumatoid arthritis: a randomized double blind study. J Rheumatol 2006; 33:659.
  82. Weinblatt ME, Schiff MH, Ruderman EM, et al. Efficacy and safety of etanercept 50 mg twice a week in patients with rheumatoid arthritis who had a suboptimal response to etanercept 50 mg once a week: results of a multicenter, randomized, double-blind, active drug-controlled study. Arthritis Rheum 2008; 58:1921.
  83. Makol A, Wright K, Matteson EL. Safe use of antirheumatic agents in patients with comorbidities. Rheum Dis Clin North Am 2012; 38:771.
  84. Raaschou P, Simard JF, Holmqvist M, et al. Rheumatoid arthritis, anti-tumour necrosis factor therapy, and risk of malignant melanoma: nationwide population based prospective cohort study from Sweden. BMJ 2013; 346:f1939.
  85. Dixon WG, Watson KD, Lunt M, et al. Influence of anti-tumor necrosis factor therapy on cancer incidence in patients with rheumatoid arthritis who have had a prior malignancy: results from the British Society for Rheumatology Biologics Register. Arthritis Care Res (Hoboken) 2010; 62:755.
  86. Chakravarty EF, Michaud K, Wolfe F. Skin cancer, rheumatoid arthritis, and tumor necrosis factor inhibitors. J Rheumatol 2005; 32:2130.
  87. Kameda T, Dobashi H, Miyatake N, et al. Association of higher methotrexate dose with lymphoproliferative disease onset in rheumatoid arthritis patients. Arthritis Care Res (Hoboken) 2014; 66:1302.
  88. Raaschou P, Frisell T, Askling J, ARTIS Study Group. TNF inhibitor therapy and risk of breast cancer recurrence in patients with rheumatoid arthritis: a nationwide cohort study. Ann Rheum Dis 2015; 74:2137.
  89. Solomon DH, Massarotti E, Garg R, et al. Association between disease-modifying antirheumatic drugs and diabetes risk in patients with rheumatoid arthritis and psoriasis. JAMA 2011; 305:2525.
  90. Haas RM, Li P, Chu JW. Glucose-lowering effects of sulfasalazine in type 2 diabetes. Diabetes Care 2005; 28:2238.
  91. Wiese AD, Griffin MR, Stein CM, et al. Opioid Analgesics and the Risk of Serious Infections Among Patients With Rheumatoid Arthritis: A Self-Controlled Case Series Study. Arthritis Rheumatol 2016; 68:323.
  92. Gaujoux-Viala C, Nam J, Ramiro S, et al. Efficacy of conventional synthetic disease-modifying antirheumatic drugs, glucocorticoids and tofacitinib: a systematic literature review informing the 2013 update of the EULAR recommendations for management of rheumatoid arthritis. Ann Rheum Dis 2014; 73:510.
  93. Nam JL, Ramiro S, Gaujoux-Viala C, et al. Efficacy of biological disease-modifying antirheumatic drugs: a systematic literature review informing the 2013 update of the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis 2014; 73:516.
  94. Schoels M, Wong J, Scott DL, et al. Economic aspects of treatment options in rheumatoid arthritis: a systematic literature review informing the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis 2010; 69:995.
  95. Ramiro S, Gaujoux-Viala C, Nam JL, et al. Safety of synthetic and biological DMARDs: a systematic literature review informing the 2013 update of the EULAR recommendations for management of rheumatoid arthritis. Ann Rheum Dis 2014; 73:529.
  96. Scott DL, Symmons DP, Coulton BL, Popert AJ. Long-term outcome of treating rheumatoid arthritis: results after 20 years. Lancet 1987; 1:1108.
  97. Wolfe F, Mitchell DM, Sibley JT, et al. The mortality of rheumatoid arthritis. Arthritis Rheum 1994; 37:481.
  98. Pincus T, Callahan LF. What is the natural history of rheumatoid arthritis? Rheum Dis Clin North Am 1993; 19:123.
  99. Harty L, O'Toole G, FitzGerald O. Profound reduction in hospital admissions and musculoskeletal surgical procedures for rheumatoid arthritis with concurrent changes in clinical practice (1995-2010). Rheumatology (Oxford) 2015; 54:666.
  100. Ajeganova S, van Steenbergen HW, van Nies JA, et al. Disease-modifying antirheumatic drug-free sustained remission in rheumatoid arthritis: an increasingly achievable outcome with subsidence of disease symptoms. Ann Rheum Dis 2016; 75:867.
  101. Krishnan E, Fries JF. Reduction in long-term functional disability in rheumatoid arthritis from 1977 to 1998:a longitudinal study of 3035 patients. Am J Med 2003; 115:371.
  102. Puolakka K, Kautiainen H, Möttönen T, et al. Early suppression of disease activity is essential for maintenance of work capacity in patients with recent-onset rheumatoid arthritis: five-year experience from the FIN-RACo trial. Arthritis Rheum 2005; 52:36.
  103. Symmons DP. Environmental factors and the outcome of rheumatoid arthritis. Best Pract Res Clin Rheumatol 2003; 17:717.
  104. 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.