Official reprint from UpToDate®
www.uptodate.com ©2018 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Disease outcome and functional capacity in rheumatoid arthritis

PJW Venables, MA, MB BChir, MD, FRCP
Ravinder N Maini, BA, MB BChir, FRCP, FMedSci, FRS
Section Editor
James R O'Dell, MD
Deputy Editor
Paul L Romain, MD


The course of rheumatoid arthritis (RA) is variable [1]. Approximately 15 to 20 percent of patients have intermittent disease with periods of exacerbation and a relatively good prognosis. However, most patients have progressive disease, with either a slow or a rapid course. The outcome of RA is dependent upon the degree of joint damage, the physical functional status of the patient, psychological health, and the presence of comorbid illness such as cardiovascular disease, infection, and B cell lymphomas. A reduced life expectancy is seen in some patients with severe RA, due to illnesses that may be the result of RA itself or the drugs used in its treatment (table 1).

Functional capacity, comorbidities, and mortality in RA are reviewed here. Cardiovascular and renal diseases associated with RA are discussed elsewhere. (See "Coronary artery disease in rheumatoid arthritis: Implications for prevention and management" and "Coronary artery disease in rheumatoid arthritis: Pathogenesis, risk factors, clinical manifestations, and diagnostic implications" and "Heart failure and left ventricular dysfunction in rheumatoid arthritis" and "Causes and diagnosis of membranous nephropathy", section on 'Drugs' and "Clinical manifestations and diagnosis of the mixed cryoglobulinemia syndrome (essential mixed cryoglobulinemia)" and "Causes and diagnosis of AA amyloidosis and relation to rheumatic diseases" and "NSAIDs: Acute kidney injury (acute renal failure)".)


Loss of functional capacity in rheumatoid arthritis (RA) is a result of the summation of loss of function in individual joints. Individual joint function depends upon numerous factors:

Severity of disease activity

Structural integrity of a joint

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Dec 2017. | This topic last updated: Oct 05, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2018 UpToDate, Inc.
  1. Lee DM, Weinblatt ME. Rheumatoid arthritis. Lancet 2001; 358:903.
  2. STEINBROCKER O, TRAEGER CH, BATTERMAN RC. Therapeutic criteria in rheumatoid arthritis. J Am Med Assoc 1949; 140:659.
  3. Wolfe F, Kleinheksel SM, Cathey MA, et al. The clinical value of the Stanford Health Assessment Questionnaire Functional Disability Index in patients with rheumatoid arthritis. J Rheumatol 1988; 15:1480.
  4. Bruce B, Fries JF. The Stanford Health Assessment Questionnaire: a review of its history, issues, progress, and documentation. J Rheumatol 2003; 30:167.
  5. Fries JF, Ramey DR. "Arthritis specific" global health analog scales assess "generic" health related quality-of-life in patients with rheumatoid arthritis. J Rheumatol 1997; 24:1697.
  6. Ramey DR, Raynauld JP, Fries JF. The health assessment questionnaire 1992: status and review. Arthritis Care Res 1992; 5:119.
  7. Fries JF, Spitz P, Kraines RG, Holman HR. Measurement of patient outcome in arthritis. Arthritis Rheum 1980; 23:137.
  8. Fries JF, Spitz PW, Young DY. The dimensions of health outcomes: the health assessment questionnaire, disability and pain scales. J Rheumatol 1982; 9:789.
  9. Ramey DR, Fries JF, Singh G. The Health Assessment Questionnaire 1995 - Status and Review. In: Pharmacoeconomics and Quality of Life in Clinical Trials, Second edition, B. Spilker (Ed), Raven Press, New York 1996. p.227-237.
  10. Meenan RF, Mason JH, Anderson JJ, et al. AIMS2. The content and properties of a revised and expanded Arthritis Impact Measurement Scales Health Status Questionnaire. Arthritis Rheum 1992; 35:1.
  11. Anderson JJ, Felson DT, Meenan RF, Williams HJ. Which traditional measures should be used in rheumatoid arthritis clinical trials? Arthritis Rheum 1989; 32:1093.
  12. 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; 42:1854.
  13. Wolfe F. A reappraisal of HAQ disability in rheumatoid arthritis. Arthritis Rheum 2000; 43:2751.
  14. Escalante A, del Rincón I. How much disability in rheumatoid arthritis is explained by rheumatoid arthritis? Arthritis Rheum 1999; 42:1712.
  15. Hawley DJ, Wolfe F. Anxiety and depression in patients with rheumatoid arthritis: a prospective study of 400 patients. J Rheumatol 1988; 15:932.
  16. Sokka T, Krishnan E, Häkkinen A, Hannonen P. Functional disability in rheumatoid arthritis patients compared with a community population in Finland. Arthritis Rheum 2003; 48:59.
  17. Lindqvist E, Saxne T, Geborek P, Eberhardt K. Ten year outcome in a cohort of patients with early rheumatoid arthritis: health status, disease process, and damage. Ann Rheum Dis 2002; 61:1055.
  18. 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.
  19. 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; 354:1932.
  20. 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.
  21. Breedveld FC, Han C, Bala M, et al. Association between baseline radiographic damage and improvement in physical function after treatment of patients with rheumatoid arthritis. Ann Rheum Dis 2005; 64:52.
  22. Chorus AM, Miedema HS, Wevers CJ, van Der Linden S. Labour force participation among patients with rheumatoid arthritis. Ann Rheum Dis 2000; 59:549.
  23. Lacaille D, Sheps S, Spinelli JJ, et al. Identification of modifiable work-related factors that influence the risk of work disability in rheumatoid arthritis. Arthritis Rheum 2004; 51:843.
  24. Puolakka K, Kautiainen H, Möttönen T, et al. Predictors of productivity loss in early rheumatoid arthritis: a 5 year follow up study. Ann Rheum Dis 2005; 64:130.
  25. 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.
  26. Walker N, Michaud K, Wolfe F. Work limitations among working persons with rheumatoid arthritis: results, reliability, and validity of the work limitations questionnaire in 836 patients. J Rheumatol 2005; 32:1006.
  27. Hazes JM, Geuskens GA, Burdorf A. Work limitations in the outcome assessment of rheumatoid arthritis. J Rheumatol 2005; 32:980.
  28. Berkanovic E, Hurwicz ML. Rheumatoid arthritis and comorbidity. J Rheumatol 1990; 17:888.
  29. Doran MF, Crowson CS, Pond GR, et al. Frequency of infection in patients with rheumatoid arthritis compared with controls: a population-based study. Arthritis Rheum 2002; 46:2287.
  30. Doran MF, Crowson CS, Pond GR, et al. Predictors of infection in rheumatoid arthritis. Arthritis Rheum 2002; 46:2294.
  31. Smitten AL, Choi HK, Hochberg MC, et al. The risk of hospitalized infection in patients with rheumatoid arthritis. J Rheumatol 2008; 35:387.
  32. Lacaille D, Guh DP, Abrahamowicz M, et al. Use of nonbiologic disease-modifying antirheumatic drugs and risk of infection in patients with rheumatoid arthritis. Arthritis Rheum 2008; 59:1074.
  33. Franklin J, Lunt M, Bunn D, et al. Incidence of lymphoma in a large primary care derived cohort of cases of inflammatory polyarthritis. Ann Rheum Dis 2006; 65:617.
  34. Wolfe F, Mitchell DM, Sibley JT, et al. The mortality of rheumatoid arthritis. Arthritis Rheum 1994; 37:481.
  35. Silman AJ, Petrie J, Hazleman B, Evans SJ. Lymphoproliferative cancer and other malignancy in patients with rheumatoid arthritis treated with azathioprine: a 20 year follow up study. Ann Rheum Dis 1988; 47:988.
  36. Wolfe F, Fries JF. Rate of death due to leukemia/lymphoma in patients with rheumatoid arthritis. Arthritis Rheum 2003; 48:2694.
  37. Zintzaras E, Voulgarelis M, Moutsopoulos HM. The risk of lymphoma development in autoimmune diseases: a meta-analysis. Arch Intern Med 2005; 165:2337.
  38. Baecklund E, Iliadou A, Askling J, et al. Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis. Arthritis Rheum 2006; 54:692.
  39. Wolfe F, Michaud K. The effect of methotrexate and anti-tumor necrosis factor therapy on the risk of lymphoma in rheumatoid arthritis in 19,562 patients during 89,710 person-years of observation. Arthritis Rheum 2007; 56:1433.
  40. Bernatsky S, Clarke AE, Suissa S. Hematologic malignant neoplasms after drug exposure in rheumatoid arthritis. Arch Intern Med 2008; 168:378.
  41. Loughran TP Jr. Clonal diseases of large granular lymphocytes. Blood 1993; 82:1.
  42. Erhardt CC, Mumford PA, Venables PJ, Maini RN. Factors predicting a poor life prognosis in rheumatoid arthritis: an eight year prospective study. Ann Rheum Dis 1989; 48:7.
  43. Kazis LE, Anderson JJ, Meenan RF. Health status as a predictor of mortality in rheumatoid arthritis: a five-year study. J Rheumatol 1990; 17:609.
  44. Pincus T, Callahan LF. Taking mortality in rheumatoid arthritis seriously--predictive markers, socioeconomic status and comorbidity. J Rheumatol 1986; 13:841.
  45. Myasoedova E, Davis JM 3rd, Crowson CS, Gabriel SE. Epidemiology of rheumatoid arthritis: rheumatoid arthritis and mortality. Curr Rheumatol Rep 2010; 12:379.
  46. Gabriel SE, Crowson CS, O'Fallon WM. Mortality in rheumatoid arthritis: have we made an impact in 4 decades? J Rheumatol 1999; 26:2529.
  47. Gabriel SE, Crowson CS, Kremers HM, et al. Survival in rheumatoid arthritis: a population-based analysis of trends over 40 years. Arthritis Rheum 2003; 48:54.
  48. Aviña-Zubieta JA, Choi HK, Sadatsafavi M, et al. Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies. Arthritis Rheum 2008; 59:1690.
  49. Meune C, Touzé E, Trinquart L, Allanore Y. Trends in cardiovascular mortality in patients with rheumatoid arthritis over 50 years: a systematic review and meta-analysis of cohort studies. Rheumatology (Oxford) 2009; 48:1309.
  50. Krishnan E, Lingala VB, Singh G. Declines in mortality from acute myocardial infarction in successive incidence and birth cohorts of patients with rheumatoid arthritis. Circulation 2004; 110:1774.
  51. Van Doornum S, Brand C, King B, Sundararajan V. Increased case fatality rates following a first acute cardiovascular event in patients with rheumatoid arthritis. Arthritis Rheum 2006; 54:2061.
  52. Warrington KJ, Kent PD, Frye RL, et al. Rheumatoid arthritis is an independent risk factor for multi-vessel coronary artery disease: a case control study. Arthritis Res Ther 2005; 7:R984.
  53. Raza K, Banks M, Kitas GD. Reversing myocardial microvascular disease in a patient with rheumatoid arthritis. J Rheumatol 2005; 32:754.
  54. van den Borne BE, Landewé RB, Houkes I, et al. No increased risk of malignancies and mortality in cyclosporin A-treated patients with rheumatoid arthritis. Arthritis Rheum 1998; 41:1930.
  55. Mellemkjaer L, Linet MS, Gridley G, et al. Rheumatoid arthritis and cancer risk. Eur J Cancer 1996; 32A:1753.
  56. Krause D, Schleusser B, Herborn G, Rau R. Response to methotrexate treatment is associated with reduced mortality in patients with severe rheumatoid arthritis. Arthritis Rheum 2000; 43:14.
  57. Choi HK, Hernán MA, Seeger JD, et al. Methotrexate and mortality in patients with rheumatoid arthritis: a prospective study. Lancet 2002; 359:1173.
  58. Myllykangas-Luosujärvi R, Aho K, Isomäki H. Death attributed to antirheumatic medication in a nationwide series of 1666 patients with rheumatoid arthritis who have died. J Rheumatol 1995; 22:2214.
  59. Wolfe F, Michaud K, Gefeller O, Choi HK. Predicting mortality in patients with rheumatoid arthritis. Arthritis Rheum 2003; 48:1530.
  60. Gonzalez A, Icen M, Kremers HM, et al. Mortality trends in rheumatoid arthritis: the role of rheumatoid factor. J Rheumatol 2008; 35:1009.
  61. Escalante A, Haas RW, del Rincón I. Paradoxical effect of body mass index on survival in rheumatoid arthritis: role of comorbidity and systemic inflammation. Arch Intern Med 2005; 165:1624.
  62. Ang DC, Choi H, Kroenke K, Wolfe F. Comorbid depression is an independent risk factor for mortality in patients with rheumatoid arthritis. J Rheumatol 2005; 32:1013.
  63. Mattey DL, Glossop JR, Nixon NB, Dawes PT. Circulating levels of tumor necrosis factor receptors are highly predictive of mortality in patients with rheumatoid arthritis. Arthritis Rheum 2007; 56:3940.
  64. Mattey DL, Thomson W, Ollier WE, et al. Association of DRB1 shared epitope genotypes with early mortality in rheumatoid arthritis: results of eighteen years of followup from the early rheumatoid arthritis study. Arthritis Rheum 2007; 56:1408.