The Facts on Rheumatoid Arthritis

Which we at Dragon Claw call Rheumatoid Disease

Sourced and summarised from the Centres for Disease Control and Prevention  While USA centric the information is very useful.

Rheumatoid Arthritis (RA)

Rheumatoid arthritis (RA) causes premature death, disability, and lowers the quality of life in the industrialized and developing world.1 RA is a systemic inflammatory disease that manifests itself in multiple joints in the body. This inflammation usually affects the lining of the joints (synovial membrane), but can also affect other organs. This inflamed joint lining leads to erosions of the cartilage and bone and sometimes causes joint deformity. Pain, swelling, and redness are common joint symptoms. RA causes are unknown, but it is believed to result from a faulty immune response. RA can begin at any age and causes fatigue and prolonged stiffness after rest. There is no cure for RA, but effective drugs are increasingly available to treat RA and prevent deformed joints. In addition to medications and surgery, scientifically-proven self-management (techniques that people use to manage their condition on a daily basis and pursue the activities important to them) approaches, such as exercise, can reduce pain and disability.

I. Background

Rheumatoid arthritis (RA), an autoimmune condition, is a chronic inflammatory polyarthritis (arthritis that affects 5 or more joints).2

The natural history of RA varies considerably with at least three possible disease courses 3-5:

  • Monocyclic: Have only one episode that ends within 2 to 5 years of initial diagnosis. This may result from early diagnosis or aggressive treatment.
  • Polycyclic: The levels of disease activity fluctuate over the course of the condition.
  • Progressive: RA continues to increase in severity and does not go away.

 Erosive changes in the bones around a joint (usually seen on an X-ray) typically occur fastest in the first year of disease.3

 One natural history study found that 75% of people with RA experienced remission within 5 years of diagnosis.4

II. Diagnosis

RA is diagnosed using information from physical examination (signs and symptoms), blood tests, and X-rays. Ideally, RA is diagnosed early - within 6 months of symptom onset - so that treatment that slows or stops disease progression can begin. Early diagnosis is challenging because the symptoms of early RA can be non-specific (that is, they can be the same for many other diseases).  Symptoms include malaise, fatigue, weakness, muscle soreness, low-grade fever, and weight loss. These symptoms may actually be caused by other conditions.6

The 2010 American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) classification criteria for rheumatoid arthritis are the standard for diagnosis and study of RA,8

Prior to the 2010 criteria, the 1987 ACR criteria were used ( Compared with the 1987 criteria, the 2010 criteria identify more people with early RA.7,8

III. Treatment

The contemporary recommended approach to treating RA is very aggressive.10 Non-biologic disease-modifying antirheumatic drugs (DMARDs), which reduce disease activity and prevent joint deformity, are prescribed within three months of diagnosis. Previously most people started with corticosteroids/non-steroidal anti-inflammatory drugs (NSAIDs), then fewer people slowly progressed to non-biologic DMARDs and even fewer people received biologic DMARDs if they did not respond to the previous drugs.

Treatment guidelines have also changed with the increased biologic DMARDs available. In 2012, the American College of Rheumatology updated RA medical management guidelines.11 These guidelines describe which biologic DMARDs to use for specific RA disease profiles (e.g., features such as disease activity, signs and symptoms, and prognosis).11

IV. Risk Factors

The etiology, or cause, of RA is unknown. Many cases are believed to result from an interaction between genetic factors and environmental exposures.2

Age and sex: The incidence of RA is typically two to three times higher in women than men. The onset of RA, in both women and men, is highest among those in their sixties.2

Genetics: There is longstanding evidence that specific HLA class II genotypes are associated with increased risk of developing RA. 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.12 More recent investigations indicate that of the more than 30 genes studied, the strongest candidate gene is PTPN22, a gene that has been linked to several autoimmune conditions.12

Modifiable: Several modifiable risk factors for RA have been studied including reproductive hormonal exposures, tobacco use, dietary factors, and microbial exposures.2

Smoking: Among the modifiable risk factors, smoking is the strongest and most consistent modifiable risk factor for RA. A history of smoking is associated with a modest to moderate (1.3 to 2.4 times) increased risk of RA onset.2 This relationship between smoking and RA is strongest among people who are ACPA-positive (anti-citrullinated protein/peptide antibodies), a maker of auto-immune activity.12

Reproductive and Breastfeeding History: Hormones related to reproduction have been studied extensively as potential risk factors for RA.

Oral Contraceptives (OC): Early studies found that women who had taken OCs had a modest to moderate decrease in risk of RA.13,14 However, most recent studies have not found a decreased risk.13-19 The estrogen concentration of contemporary OCs is typically 80%-90% lower than the first OCs introduced in the 1960s.16 This may account for the lack of associations in recent studies.16

Hormone Replacement therapy (HRT): There is mixed evidence of an association between HRT and RA onset. 16, 20-24

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. 19, 21, 23, 24

Breastfeeding: Almost all recent population based studies have found that RA is less common among women who breastfeed.16,24-26

Menstrual History: At least two studies have observed that women with irregular menses or a truncated menstrual history (e.g., early menopause) have an increased risk of RA.21,23 Because women with polycystic ovarian syndrome (PCOS) have an increased risk of RA, the association with an irregular menstrual history may result from PCOS.23

Early Life Exposures: Early life exposures may alter risk of developing RA in adulthood.25  For example, one study found that maternal smoking doubled the risk of children developing RA as adults.26 The relationship between birthweight and later onset of RA is inconsistent: one study found no effect while others have found that both low and high birth weight are risk factors.25 Lower socio-economic status in childhood has been linked to heightened risk of developing RA.26

Physical Activity: The only study examining the role of physical activity in the development of RA found a dose response relationship; that is, the risk of RA declined with increasing levels of leisure time physical activity. However, the risk ratios were not statistically significant.27

Vitamin D: Two studies examining vitamin D as a risk factor for RA onset found no associations.28,29  

V.  Prevalence

Internationally, the prevalence of RA is believed to range from 0.4 to 1.3%.2,32

In 2005, an estimated 1.5 million (0.6%) of US adults age ≥ 18 had RA.33,35

The prevalence of RA, at least among women, may be increasing.  The most recent US data on the prevalence of RA is from the Rochester Epidemiology Project in Minnesota. This ongoing  study provides the majority of population-based descriptive statistics on RA.33 

In 2005, the age-standardized prevalence of RA among women in the Rochester Epidemiology Project had increased to 1% (9.8 per 1,000) from 0.8% (7.7 per 1,000) in 1995.  The prevalence among men was the same (0.4%) in 1995 and 2005 (4.1 per 1,000 in 1995 and 4.4  per 1,000 in 2005).33

Another study, in Ontario, Canada, reported an increase in RA prevalence among both women and men from 1996 to 2010.34 This increase has been attributed to increasing emphasis on early diagnosis and treatment of RA34, and environmental changes.33

VI. Incidence

The Rochester Epidemiology Project provides the most recent US data on the incidence of RA.33  In 1995-2007, 41 per 100,000 people were diagnosed with RA annually. Incidence rose with age (e.g., 8.7 per 100,000 people among those aged 18-34 years compared with 54 per 100,000 among those age ≥ 85 years) and peaked at age 65-74 years (89 per 100,000); all estimates age-adjusted to 2000 US population. From 1995 to 2007, rates increased by 2.5% each year among women but there was a small decrease (0.5%) among men.33

In longitudinal study of RA in the Rochester Epidemiology Project, incidence among women and men was highest at the beginning of the project in 1955, but declined to its lowest in the late 1980s and early 1990s.33

At least one study found that incidence was the same regardless of whether cases were defined using the 1958 American Rheumatology Association or 1987 American College of Rheumatology definition.35

VII. Lifetime Risk

The lifetime risk of rheumatoid arthritis in the Rochester Minnesota Epidemiology was an estimated 4% among women and 3% among men.36

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VIII. Mortality

In 1997, RA accounted for 22% of all deaths due to arthritis and other rheumatic conditions in the United States.37

Multiple studies report that in the past half century, mortality among people with diagnosed RA has increased compared with the general population.38

Around 40% of all deaths in individuals with RA are attributable to cardiovascular causes, including ischemic heart disease and stroke. The most recent North American study of mortality among people with RA, based on 1965–1990 data, found a standardized mortality ratio of 2.3 among people with RA compared with the general population;39 that is, people with RA were twice as likely to die as people of the same age in the general population.

Among people with RA, the presence of rheumatoid factor (RF) and/or anti-citrullinated protein antibody (ACPA) are potential markers of premature death.36

Weight loss was a strong predictor of mortality in another study.40 

IX. Comorbidities

The four most common comorbidities among people with arthritis, in order of prevalence are the following:

1      Cardiovascular disease (CVD), in particular ischemic heart disease, is more common among people with RA.38 It is unclear whether the risk of CVD is before the disease or results from it; a Rochester Epidemiology Project study found that people with RA were more likely to have a hospitalization because of myocardial infarction (MI) prior to diagnosis.38 However, two longitudinal cohort studies have found no difference in presence of MI, congestive heart failure or angina prior to diagnosis of RA.38 People with RA have greater evidence of subclinical atherosclerotic disease,41 and risk of silent MI.42 A 2015 study found that risk of CVD rose with increasing levels of disease activity.43 

2      It is unknown whether the increase in CVD mortality is due to the disease, 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.41, 44

3      Infections, most commonly tuberculosis, are another important and primary cause of death among people with RA. Infections may be responsible for 25% 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.41, 44

4      Mental health conditions: High prevalence of anxiety and depression has been documented in several clinical populations of people with RA. Both conditions are associated with increased disease activity and decreased physical function and adherence to medical and non-medical interventions.45-48

5      Malignancies: People with RA have an increased incidence of lymphoproliferative malignancies (such as leukemia and multiple myeloma). The cause of this increase is unknown.44

X. Hospitalisations

In 2012, there were 9,100 hospitalizations with RA listed as the principal diagnosis with total hospital charges of $374 million (mean charge of $41,000 per person) (2012 Nationwide Inpatient Survey).49 Women and people aged 45 years and older accounted for the majority of these stays.49

All cause hospitalization in Rochester Minnesota from 1980 to 2007 was higher among people with RA among those without RA.50 

XI. Ambulatory Care

In 2007, there were 2.9 million ambulatory care visits in the United States among people with RA. Most of these were physician office visits (2.6 million) with 1.9 million visits to medical specialty offices (e.g., rheumatologists).51

XII. Costs

Medical costs attributable to RA in the 2005 US Medical Expenditure Panel Survey (MEPS), were 22.3 billion ($2,085 per person).52 MEPS is a nationally representative survey of civilian and non-institutionalized population.

Indirect costs: Earnings losses attributable to RA in the 2006 MEPS were $1,212 per person.53 

One study examined RA-attributable costs to patients, employers, family members, and the government reported total costs of $39.2 billion (2005 US dollars) 54:

  • Direct costs (out-of-pocket medical expenditures paid by patients, family members, and government) were $8.4 billion.54
  • Indirect costs (earnings losses, expenditures for adapting physical home and work environments, disability payments borne by employers and government, decreased productivity and cost of retraining replacement workers) were $10.9 billion.54
  • Intangible costs (premature mortality and deterioration in quality of life) were $39.2 billion.54

Lifetime costs: Using Rochester Epidemiology Project data, Gabriel et al. also estimated the median lifetime costs (i.e., 25 years following a diagnosis of RA) of RA to be $61,000 to $122,000 (US 1995 dollars).  Lifetime costs were highest among younger people with RA.55

XIII. Impact on Health-Related Quality of Life (HRQOL) and Work

People with RA have worse functional status than those with osteoarthritis, and those without arthritis.56

One study examining the self-reported quality of life found that compared with those without arthritis, people with RA were

       40% more likely to report fair or poor general health (odds ratios [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).

       Twice as likely to have a health-related activity limitation (OR=2.0, 95% CI=1.7, 2.4).57

People with RA may experience more losses in function than people without arthritis in every domain of human activity including work, leisure and social relations.58 Work loss among people with RA is highest among people 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.59

Numerous studies indicate that RA can have a substantial negative impact on the work lives of people with RA.  For example, an analysis of Rochester Minnesota Epidemiology Project data indicated that the typical work experience of people with RA differed substantially from those without arthritis.56 Compared with people without arthritis, people with RA were more likely to do the following:

       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%).

       Be unable to find a job (15.3% vs 5.2%). 

Early and aggressive medical treatment of RA may reduce work disability.60


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