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National Center for Chronic Disease Prevention and Health Promotion

Division of Adult and Community Health
Health Care and Aging Studies Branch

Arthritis Program
Mailstop K-51
4770 Buford Highway NE
Atlanta, GA 30341-3724
Phone: 770.488.5464
Fax: 770.488.5964
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Arthritis Types — Overview
Arthritis Basics

bullet Arthritis Types — Overview
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bullet Risk Factors
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bullet Frequently Asked Questions (FAQs)
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bullet Arthritis: At A Glance


Rheumatoid Arthritis

Content Overview:  

I. Background

  • Rheumatoid arthritis (RA), an autoimmune condition, is a chronic inflammatory polyarthritis.1
     
  • Natural history studies of RA suggests that RA follows one of three courses
    • Monocyclic in 20% of people initially diagnosed with RA (i.e., had one episode which abated within two years of initial presentation and did not reoccur).
    • Polycyclic in 70% (i.e., fluctuating levels of disease activity).
    • Progressive and unremitting condition in 10%.3

    Another natural history study found that 75% of people with RA experienced remission after five years.4
     

  • Historically, pharmacologic treatment of RA has traditionally followed the pyramid approach. That is, treatment starts with corticosteroids/non-steroidal anti-inflammatory drugs, then progresses to disease-modifying antirheumatic drugs (DMARD) and finally to biologic response modifiers (BRM) if persons are non-responsive to the previous drugs. Today, a more aggressive treatment approach is being advocated for people with early RA, with prescription of DMARDs within three months of diagnosis.1
     
  • Diagnosis
    • The 1987 American College of Rheumatology* criteria are used in the clinical diagnosis of RA, and to define RA in epidemiologic studies. Persons must meet four of seven ACR criteria;5 these criteria are based on clinical observation (e.g., number of joints affected), laboratory tests (e.g., positive rheumatoid factor), and radiographic examination (e.g., X-rays evidence of joint erosion).5
    • Early RA is typically defined as RA that is diagnosed within 6 months of symptom onset. There is extensive interest in early diagnosis of RA because early treatment may improve disease prognosis. The only U.S. study to examine time between symptom onset and diagnosis reported a median lag time of approximately 4 weeks between symptom onset and medical encounter, and a median time of 18 weeks between medical encounter and RA diagnosis (A total median lag time of 36 weeks)6. These authors noted that there was even a delay in diagnosing patients with most identifiable features of RA (e.g., morning stiffness and seropositive rheumatoid factor), and concluded that early disease recognition is challenging as only half of those who eventually develop RA initially present with features specific to the condition.
       
  • Risk factors
    • A range of environmental and genetic variables have been evaluated as potential risk factors for RA (e.g. hormonal exposures, tobacco use, dietary components, HLA genotype, and microbial exposures), but to date no definitive risk factors for RA have been identified.
    • Of the environmental factors examined, the most consistent evidence exists for an association between tobacco use and RA; most studies of this risk factor have found a history of smoking is associated with RA onset with increased risks ranging from 1.3 to 2.4.2
    • The role of the following four estrogenic factors in RA etiology has been studied extensively:
      • Oral contraceptives(OC) — Early studies found a decreased risk of RA among women who had ever used OCs, a relationship that has not been confirmed in recent studies.19-21
      • Hormone replacement therapy (HRT) — There is mixed evidence of an association between HRT and RA onset.20-25
      • Live birth history — Most studies have found that women who have never had a live birth have a slight to moderately increased risk of RA.21,24,26,27
      • Breastfeeding — The most recent studies have found that RA is less common among women who breastfeed; this is in contrast with earlier studies which found an increased risk associated with breastfeeding.21,28-30
    • Genetic susceptibility markers. Most attention has been given to the DR4 and DRB1 molecules of the major histocompatability complex HLA class II genes. The strongest associations have been found between RA and the DRB1*0401 and DRB1*0404 alleles.2

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II. Prevalence

  • An estimated 1.293 million adults aged 18 and older (0.6%) had RA in 2005, down from the previous 1990 estimate of 2.1 million.40 This is partly due to a more restrictive definition of RA, but in part reflects well established declines in RA prevalence around the world.
     
  • The prevalence among women in 1995 was approximately double that in men (1.06% versus 0.61%).40
     
  • This study observed almost a 2:1 ratio in prevalence for women to men (1,367 per 100,000 (95% CI=1,175-1,558) among women compared with 736 per 100,000 (95% CI=561-912) in men.8)
     
  • Prevalence decreasing.

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III. Incidence

  • The incidence of RA is typically two to three times higher in women than men. Incidence studies from three populations show that incidence of RA in both women and men peaks in their sixties.2
     
  • The observed incidence of RA in the United States ranges from 42 people per 100,000 (95% CI=23-60) (years 1987–1990)9 to 68.3 persons per 100,000 (95% CI=57.2-79.5) (years 1975–1985)8 depending on the definition used. Another study found incidence to be the same regardless of the definition (i.e., 1958 American Rheumatology Association, and 1987 American College of Rheumatology definitions).10
     
  • Incidence has ranged from 24 persons per 100,000 (95% CI=19-30)10 to 88.1 persons per 100,000 (95% CI=71.0-105.3)8 among women,8 and rates of 22 persons per 100,000 (95% CI=13-32)9 to 46.8 persons per 100,000 (95% CI=32.4-61.2) among men.8
     
  • There is some evidence that the incidence of RA in the United States is declining. Between 1955–1964 the annual incidence of RA in the Olmsted County population was 90.2 persons per 100,000 (95% CI=75.1-105.3) whereas the annual incidence declined to 68.3 persons per 100,000 for the interval 1975–1985 (95% CI=57.2-79.5).8

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IV. Mortality

  • In 1997, RA accounted for 22% of all deaths due to arthritis and other rheumatic conditions.11
     
  • The most recent North American study of mortality among people with RA, based on data from 1965–1990, found a standardized mortality ratio of 2.26 among people with RA compared to the general population.12 That is, people with RA are two times more likely to die than people of the same age in the general population.
     
  • Co-morbidities
    • Cardiovascular disease (CVD) is responsible for approximately half of all deaths among people with RA.17 The incidence of CVD among people with RA is similar to that of people without the condition,17 although people with RA have greater evidence of subclinical atherosclerotic disease.18 It is unknown whether the increase in CVD mortality is due to the risk factor profile of people with RA (e.g., presence of hypertension, more likely to be smokers), or the effects of the drugs used to treat the condition.17,18
    • Infections have also been cited as another important and primary cause of death among people with RA; infections may be responsible for one-quarter of deaths among people with RA. It is unclear whether this increased susceptibility arising from immunosuppression is due to the intrinsic immune dysfunction in people with RA, the effects of the drugs used to treat it, or both.17,18
    • An increased incidence of lymphoproliferative malignancies (such as leukemia and multiple myeloma) has also been reported among people with RA. The cause of this increase is unknown.17

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V. Hospitalizations

  • In 2004, there were 20,000 hospitalizations with RA as the principal diagnosis in the Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Sample.35 Eighty-five percent of these hospitalizations were among people aged 45 years or older. Women accounted for 15,000 of the hospitalizations.

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VI. Ambulatory Care

  • In 1997, there were 3,978,000 ambulatory care visits in the United States among people with RA. This comprised 10.9% of all visits among people with arthritis and other rheumatic diseases.36 [These estimates were drawn from the National Ambulatory Medical Care and National Hospital Ambulatory Medical Care Surveys.]
     
  • The majority of these ambulatory care visits were to physician offices (3,566,000 visits) while the remaining were outpatient visits (392,000 visits).36

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VII. Costs

Direct and indirect costs

  • A study of direct (i.e., medical) costs among people with RA at the Mayo Clinic found an average cost of $3,802.05 (in U.S. dollars) per person in the year 1987 ($5,763.32 in U.S. 2000 dollars).31 These authors also reported that people with RA were approximately six times (odds ratio=6.4, 95% CI=5.4, 7.7) more likely than people without arthritis to incur medical charges. These charges were not just for musculoskeletal disorders but for care of disorders of most body systems.
     
  • Gabriel et al., reported, in a 1992 study of indirect costs, that indirect and non-medical expenditures for a person with RA were $2269 per year ($2784.90 in U.S. 2000 dollars) compared to $824 ($1011.35 in U.S. 2000 dollars) for a person with osteoarthritis, and $816 ($1001.53 in U.S. 2000 dollars) per persons without arthritis.32
     
  • In the same study, they reported that the typical work experience of people with RA differed substantially from that of someone without arthritis. Compared with people without arthritis, people with RA were more likely to do the following due to illness: change occupation (3.3% vs 0%), reduce work hours (12.2% vs 1.7%), lose their job (3.3% vs 0%), retire early (26.3% vs 5.2%), and be unable to find a job (15.3% vs 5.2%).32
     
  • A recent Canadian survey found that the average direct and indirect costs among people with RA were $6777 ($4679 in direct costs and $2098 in indirect costs) (in U.S. 2000 dollars).33 This study was based on a population sample of family physicians and rheumatologists. Costs associated with RA were almost twice of those for osteoarthritis.

Lifetime costs

  • Gabriel et al., (1998) also estimated the median lifetime costs (i.e., 25 years following a diagnosis of RA) of RA to be $61,000 to $122,000 (U.S. 1995 dollars) (lifetime costs were highest among younger people with RA).34

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VIII. Impact on health-related quality of life (HRQOL)

  • The functional status of people with RA has been observed to be compromised relative to those without the condition. People with RA have worse functional status than those with osteoarthritis, and those without arthritis.32
     
  • One study examining the self-reported quality of life among people with RA compared to people without arthritis those found that those with RA were 40% more likely to report fair or poor general health (OR=1.4, 95% CI=1.2, 1.6), 30% more likely to need help with personal care (OR=1.3, 95% CI=1.1, 1.5), and twice as likely to have a health-related activity limitation (OR=2.0, 95% CI=1.7, 2.4)37 compared with those without arthritis.
     
  • People with RA have been reported to experience more losses in function than people without arthritis in every domain of human activity including work, leisure and social relations.38 Work loss among people with RA has observed to be highest among persons among service workers, and lower among those in jobs with few physical demands, or in jobs where they have influence over the job pace and activities.39

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IX. References

  1. Guidelines for the management of rheumatoid arthritis: 2002 Update. Arthritis Rheum 2002;46(2):328–346.
  2. Silman A. Rheumatoid arthritis. In: Silman A, Hochberg MC, editors. Epidemiology of the Rheumatic Diseases. Oxford University Press, 2001;31–71.
  3. Masi AT, Maldonado-Cocco JA, Kaplan SB, Feigenbaum SL, Chandler RW. 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(4):299–326.
  4. Pincus T, Callahan LF. What is the natural history of rheumatoid arthritis? Rheum Dis Clin North Am 1993;19(1):123–151.
  5. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;31(3):315–324.
  6. Chan KW, Felson DT, Yood RA, Walker AM. The lag time between onset of symptoms and diagnosis of rheumatoid arthritis. Arthritis Rheum 1994;37(6):814–820.
  7. Rasch EK, Hirsch R, Paulose-Ram R, Hochberg MC. Prevalence of rheumatoid arthritis in persons 60 years of age and older in the United States: effect of different methods of case classification. Arthritis Rheum 2003;48(4):917–926.
  8. Gabriel SE, Crowson CS, O'Fallon WM. The epidemiology of rheumatoid arthritis in Rochester, Minnesota, 1955-1985. Arthritis Rheum 1999;42(3):415–420.
  9. Chan KW, Felson DT, Yood RA, Walker AM. Incidence of rheumatoid arthritis in central Massachusetts. Arthritis Rheum 1993;36(12):1691–1696.
  10. Dugowson CE, Koepsell TD, Voigt LF, Bley L, Nelson JL, Daling JR. Rheumatoid arthritis in women. Incidence rates in group health cooperative, Seattle, Washington, 1987-1989. Arthritis Rheum 1991;34(12):1502–1507.
  11. Sacks JJ, Helmick CG, Langmaid G. Deaths from arthritis and other rheumatic conditions, United States, 1979–1998. J Rheumatol 2004;31(9):1823–1828.
  12. Wolfe F, Mitchell DM, Sibley JT, Fries JF, Bloch DA, Williams CA et al. The mortality of rheumatoid arthritis. Arthritis Rheum 1994;37(4):481–494.
  13. Reilly PA, Cosh JA, Maddison PJ, Rasker JJ, Silman AJ. Mortality and survival in rheumatoid arthritis: a 25 year prospective study of 100 patients. Ann Rheum Dis 1990;49(6):363–369.
  14. Kroot EJ, van Leeuwen MA, van Rijswijk MH, Prevoo ML, 't Hof MA, van De Putte LB et al. No increased mortality in patients with rheumatoid arthritis: up to 10 years of follow up from disease onset. Ann Rheum Dis 2000;59(12):954–958.
  15. Lindqvist E, Eberhardt K. Mortality in rheumatoid arthritis patients with disease onset in the 1980s. Ann Rheum Dis 1999;58(1):11–14.
  16. Bjornadal L, Baecklund E, Yin L, Granath F, Klareskog L, Ekbom A. Decreasing mortality in patients with rheumatoid arthritis: results from a large population based cohort in Sweden, 1964–1995. J Rheumatol 2002;29(5):906–912.
  17. Mikuls TR, Cerhan JR, Criswell LA, Merlino L, Mudano AS, Burma M et al. Coffee, tea, and caffeine consumption and risk of rheumatoid arthritis: results from the Iowa Women's Health Study. Arthritis Rheum 2002;46(1):83–91.
  18. Wasko MC. Comorbid conditions in patients with rheumatic diseases: an update. Curr Opin Rheumatol 2004;16(2):109–113.
  19. Brennan P, Bankhead C, Silman A, Symmons D. Oral contraceptives and rheumatoid arthritis: results from a primary care-based incident case-control study. Semin Arthritis Rheum 1997;26(6):817–823.
  20. Doran MF, Crowson CS, O'Fallon WM, Gabriel SE. The effect of oral contraceptives and estrogen replacement therapy on the risk of rheumatoid arthritis: a population based study. J Rheumatol 2004;31(2):207–213.
  21. Karlson EW, Mandl LA, Hankinson SE, Grodstein F. Do breast-feeding and other reproductive factors influence future risk of rheumatoid arthritis? Results from the Nurses' Health Study. Arthritis Rheum 2004;50(11):3458–3467.
  22. Carette S, Marcoux S, Gingras S. Postmenopausal hormones and the incidence of rheumatoid arthritis. J Rheumatol 1989;16(7):911–913.
  23. Koepsell TD, Dugowson CE, Nelson JL, Voigt LF, Daling JR. Non-contraceptive hormones and the risk of rheumatoid arthritis in menopausal women. Int J Epidemiol 1994;23(6):1248–1255.
  24. Merlino LA, Cerhan JR, Criswell LA, Mikuls TR, Saag KG. Estrogen and other female reproductive risk factors are not strongly associated with the development of rheumatoid arthritis in elderly women. Semin Arthritis Rheum 2003;33(2):72–82.
  25. Hernandez-Avila M, Liang MH, Willett WC, Stampfer MJ, Colditz GA, Rosner B et al. Exogenous sex hormones and the risk of rheumatoid arthritis. Arthritis Rheum 1990;33(7):947–953.
  26. Spector TD, Roman E, Silman AJ. The pill, parity, and rheumatoid arthritis. Arthritis Rheum 1990;33(6):782–789.
  27. Pope JE, Bellamy N, Stevens A. The lack of associations between rheumatoid arthritis and both nulliparity and infertility. Semin Arthritis Rheum 1999;28(5):342–350.
  28. Brennan P, Silman A. Breast-feeding and the onset of rheumatoid arthritis. Arthritis Rheum 1994;37(6):808–813.
  29. Brun JG, Nilssen S, Kvale G. Breast feeding, other reproductive factors and rheumatoid arthritis. A prospective study. Br J Rheumatol 1995;34(6):542–546.
  30. Jorgensen C, Picot MC, Bologna C, Sany J. Oral contraception, parity, breast feeding, and severity of rheumatoid arthritis. Ann Rheum Dis 1996;55(2):94–98.
  31. Gabriel SE, Crowson CS, Campion ME, O'Fallon WM. Direct medical costs unique to people with arthritis. J Rheumatol 1997;24(4):719–725.
  32. Gabriel SE, Crowson CS, Campion ME, O'Fallon WM. Indirect and nonmedical costs among people with rheumatoid arthritis and osteoarthritis compared with nonarthritic controls. J Rheumatol 1997;24(1):43–48.
  33. Maetzel A, Li LC, Pencharz J, Tomlinson G, Bombardier C. The economic burden associated with osteoarthritis, rheumatoid arthritis, and hypertension: a comparative study. Ann Rheum Dis 2004;63(4):395–401.
  34. Gabriel SE, Crowson CS, Luthra HS, Wagner JL, O'Fallon WM. Modeling the lifetime costs of rheumatoid arthritis. J Rheumatol 1999;26(6):1269–1274.
  35. H-CUPnet. Patient and hospital characteristics for ICD-9-CM principle diagnosis code(s) 714.0–714.9. http://hcupnet.ahrq.gov/HCUPnet.asp. Accessed June 4, 2007.
  36. Hootman JM, Helmick CG, Schappert SM. Magnitude and characteristics of arthritis and other rheumatic conditions on ambulatory medical care visits, United States, 1997. Arthritis Rheum 2002;47(6):571–581.
  37. Dominick KL, Ahern FM, Gold CH, Heller DA. Health-related quality of life among older adults with arthritis. Health Qual Life Outcomes 2004;2(1):5.
  38. Yelin E, Lubeck D, Holman H, Epstein W. The impact of rheumatoid arthritis and osteoarthritis: the activities of patients with rheumatoid arthritis and osteoarthritis compared to controls. J Rheumatol 1987;14(4):710–717.
  39. Yelin E, Henke C, Epstein W. The work dynamics of the person with rheumatoid arthritis. Arthritis Rheum 1987;30(5):507–512.
  40. Helmick CG, Felson DT, Lawrence RC, Gabriel S, Hirsch R, , Kwoh CK, Liang MH, Maradit Kremers H, Mayes MD, Merkel PA, Pillemer SR, Reveille JD, and Stone JH for the National Arthritis Data Workgroup. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States: Part I. Arthritis Rheum 2008;58(1):15–25.

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X. Resources

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Page last reviewed: July 30, 2007
Page last modified: January 11, 2008
Content Source: Division of Adult and Community Health, National Center for Chronic Disease Prevention and Health Promotion


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