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Evidence to Support the National Action Plan for Osteoarthritis, Rheumatoid Arthritis and Osteoporosis: Opportunities to Improve Health-

Related Quality of Life and Reduce the Burden of Disease and Disability 35

5. Rheumatoid Arthritis

5.1 Overview

Rheumatoid arthritis is a chronic, autoimmune, inflammatory joint disease of unknown causeaffecting approximately 1% of the population worldwide. Without early disease-modifyingtreatment, progressive and irreversible joint damage can occur that results in lifelongfunctional impairment. Rheumatoid arthritis can have a severe impact on health-relatedquality of life and socio-economic status and is associated with premature death (Blumenaueret al 2003).

Optimal management of rheumatoid arthritis involves arresting or controlling the progression

of the disease through early diagnosis and early treatment with disease-modifying therapy,and support to manage the physical, social, emotional and occupational sequelae. This reportoutlines opportunities to improve the prevention and management of rheumatoid arthritis. Thefindings are summarised in Figure 5.1.

Prevention and management of rheumatoid arthritis acrossthe disease continuum

Figure 5.1: Summary of opportunities to improve rheumatoid arthritis prevention andmanagement

Disease continuum

Stage ofdisease

continuum

Wellpopulation

At risk population Establisheddisease

Controlled chronicdisease

Level ofprevention

Primaryprevention

Secondary prevention/ early detection Disease management and tertiary

prevention

GoalPreventincidentdisease

Prevent progression toestablished disease

Prevent repeatedacute episodes,

readmissions, andprevent or delay

complications

Optimise health-relatedquality of life

Nature ofintervention

*Promoteawareness ofthe risks ofsmoking

*Knowledgeable healthprofessionals

*Ensure early recognitionof symptoms andprompt referral tospecialist

*Initiate disease-modifying therapy early

*Support attendance atan educational program

*Consider occupationalintervention

*Monitor diseaseactivity andoptimise therapy

*Manage co-morbidities

*Provide timelyaccess to jointreplacementsurgery

*Monitor diseaseactivity and optimisetherapy

*Optimise symptomrelief

*Support ongoing self-management

*Preserve function andindependence

*Provide psychosocialsupport

*Provide access tomulti-disciplinary care

Responsiblesectors

*Public health*Primary care*Other sectors

*Primary care*Specialist services*Community care

*Specialistservices

*Hospital care*Primary care

*Primary care*Community care

Promotion ofHRQOL

HealthPromotion

Health Promotion Health Promotion Health Promotion

NB Each stage requires critical assessment of: workforce requirements, resource allocation, data requirements,evidence base, cost-effectiveness, quality measures, guidelines and standards, monitoring and evaluation, roles andresponsibilities (National, State, public/private), equity impact, consumer involvement etc.

Source: Adapted from the National Public Health Partnership group framework (2001)

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Identifying rheumatoid arthritis

Early diagnosis is of paramount importance as prompt initiation of disease-modifyingtreatment can limit the joint damage that occurs in rheumatoid arthritis (Kim and Weisman

2000). However, identification of early rheumatoid arthritis is difficult because of the lack ofdisease-specific early-onset features (Schumacher et al 2003). There is no single specific sign,symptom or diagnostic feature that distinguishes early rheumatoid arthritis from other formsof inflammatory arthritis. Methods to detect rheumatoid arthritis include clinical assessment,imaging and laboratory tests. Clinical assessment and opinion is considered the goldstandard (Symmons 2002).

Imaging

Joint damage from rheumatoid arthritis can be seen on conventional x-ray and there aremethods to score and report the level of structural involvement. Magnetic resonance imaging

and ultrasound can aid visualisation of early changes that would not be seen on conventionalx-ray, however, they require validation and further refinement (Goldblach-Mansky et al 2003;Schumacher et al 2003). The clinical relevance of radiological assessment has not beendefined (Scott et al 2003).

Laboratory tests

The detection of rheumatoid factor has been central to diagnosing rheumatoid arthritis andpredicting its course; however, the test is non-specific and has low sensitivity in patients withearly or recent onset disease (Hueber et al 2003; Cush 2003). Rheumatoid factor is negative in

between 20% and 30% of patients throughout the duration of rheumatoid arthritis (Sokka2003). Synovial fluid analysis may help to eliminate other possible causes of inflammatory

arthritis; however, there is no defining feature that allows diagnosis of rheumatoid arthritis(Schumacher et al 2003).

Clinical assessment

There are limitations to relying on history and physical examination to diagnose rheumatoidarthritis because of the lack of disease-specific features. Classification criteria to distinguishrheumatoid arthritis from other forms of inflammatory arthritis have been developed (Arnettet al 1988); however, they are less valid in early rheumatoid arthritis and were not designed asa diagnostic tool (Schumacher et al 2003). Timely access to specialist care improves the

potential for correct identification of rheumatoid arthritis in its early stages (Schumacher et al

2003).

Natural history and disease progression

Clinical presentation

The onset of rheumatoid arthritis is usually gradual, although it may be acute. Pain, swellingand stiffness may affect one or more joints, usually of the upper or lower limbs. Generalfeatures including fatigue, weakness, general malaise or fever. It is difficult to distinguish theonset of persistent rheumatoid arthritis from other self-limiting forms of inflammatory

arthritides (Ollier et al 2001). Although the onset of the condition may occur at any age, the

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peak incidence of rheumatoid arthritis occurs between the ages of 55 and 64 years in womenand between 65 and 75 years in men (Symmons 2002).

Radiological progression

While radiological changes may be negligible in early rheumatoid arthritis (Dixey et al 2004),there is evidence that the disease can progress rapidly in the early stages to cause irreversible

joint damage (Landewe and van der Heijde 2003). At baseline, joint damage is evident on x-ray in approximately 30% of people, and is more extensive in the first year than in the secondand third years (van der Heijde et al 1995). Radiological progression appears to be linear(Dixey et al 2004).

Baseline predictors of radiological progression in rheumatoid arthritis include older age,female gender, rheumatoid factor-positivity, longer disease duration, increased pain andinflammation (Ollier et al 2001). An initial, high rheumatoid factor titre (level) is thedominant predictor of erosive bone damage (Scott 2004). People with active, rheumatoidfactor-positive disease involving more than one joint, have a 70% chance of developing joint

damage within two to three years of the onset of rheumatoid arthritis (Scott 2000; Brook andCorbett 1977; Fuchs et al 1989; Mottonen 1988; van der Heijde et al 1992; Plant et al 1994;Combe et al 2003; Dixey et al 2004). The wrists are most commonly involved (Scott 2004).After five years, between 39% and 73% of affected people have evidence of joint damage intheir hands and wrists (Scott et al 2003).

Radiological damage progresses throughout the course of rheumatoid arthritis, although therate and degree of joint damage varies from person to person (Combe et al 2003). The averagerate of increase in radiological progression is approximately 2% maximal damage per year(Scott 2004). After 20 years, people with rheumatoid arthritis have an average of 43% ofmaximum possible joint damage (Scott et al 2003). Healing of erosive bone damage has beenreported, but is a rare occurrence.

Functional decline

Longitudinal data demonstrate a progressive and fairly rapid loss of function among peoplewith rheumatoid arthritis. The greatest decline in function generally occurs within the firsttwo years of disease onset (Hallert et al 2003), and after progressing quickly, the rate offunctional decline tapers off (Wolfe and Cathey 1991). Severe functional deterioration is seenin 10% of people at two years and up to 50% of people are work disabled after ten years(Wolfe and Hawley 1998; Sokka et al 1999). Female gender, older age and lower educationallevel are associated with worse disability (Leigh et al 1992). Age is the best predictor of

physical disability in both males and females (Kuiper et al 2001).

One study showed that after five years, 10% of people required home adaptations or requiredregular use of a wheelchair, 18% needed mobility aids, 17% of people had undergonereconstructive surgery and 8% had undergone major joint replacement surgery (Young et al2000). More than 50% of people with rheumatoid arthritis are unable to perform householdchores and the majority (60%) receive unpaid help (Maetzel et al 2004). After 20 years, 25%of people with rheumatoid arthritis have had joint replacement surgery (Wolfe and Zwillich1998).

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Prognostic risk factors

The characteristics of disease presentation can predict the course of the disease. Acute onsetwith fever, evidence of recent infection, fewer involved joints and good functional statusaccording to self-report and objective measures are associated with a better outcome in

rheumatoid arthritis (Pincus et al 1994; Schumacher et al 2003).

The following are prognostic features associated with the development of progressive andsevere rheumatoid arthritis:

Involvement of more than one joint (Pincus et al 1994; Wolfe et al 1993; Mitchell etal 1986);

High erythrocyte sedimentation rate or C-reactive protein at outset (Kaarela andKautiainen 1997; Devlin et al 1997; van der Heijde et al 1992; van Leeuwen et al1994);

Positive rheumatoid factor (Wolfe et al 1993; van Schaardenburg et al 1993; Paimelaet al 1995; Wolfe and Hawley 1985);

Evidence of early radiological changes (Corbett et al 1993); Poor functional scores at outset (Pincus et al 1994; Wolfe et al 1993; Eberhardt and

Fex 1995; Leigh and Fries 1992); Adverse socio-economic circumstances and lower educational level (Callahan and

Pincus 1988; Callahan et al 1996; McEntegart et al 1997; Maiden et al 1999).

Treatment goals

The ultimate aim in treating rheumatoid arthritis is to induce complete remission.Other treatment goals include minimising joint damage and functional loss, alleviating

pain and maximising quality of life (ACR 2002). This can be achieved through theearly introduction of disease-modifying drug therapy, education to assist individualsin the day to day management of their condition, rehabilitation, and a comprehensiveapproach to the provision of care and support.

KEY OBJECTIVE: Promote best practice for the optimal management of rheumatoidarthritis.

Juvenile arthritisJuvenile arthritis, also known as juvenile idiopathic arthritis, juvenile rheumatoid arthritis and

juvenile chronic arthritis, is the most common rheumatoid disease in children (Manners andBower 2002). There are several different types of juvenile arthritis and the prognosis variesaccording to each particular form of the disease. The disease primarily affects the knee, ankle,elbow, wrist and hand and can lead to serious outcomes including severe arthritis, eye damageand blindness and in some cases, death (White 2003).

While juvenile arthritis is markedly different from adult rheumatoid arthritis, the goals ofmanagement are similar, including reduction of joint inflammation, pain relief, prevention ofdisability and maintenance of function, the provision of education and attention to

psychosocial and growth and development needs. A multi-disciplinary approach is required todeliver a comprehensive and effective program (Prieur 2003).

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Many young people develop joint damage as a result of juvenile arthritis and continue toexperience the effects of the disease into adulthood. A significant proportion will developsevere physical disability (Ravelli 2004; Duffy 2004). Thus, there is a need to ensure that the

process of transition from child-centred to adult-oriented care is planned and managed

effectively (Petty 2003).

Incidence and prevalence

A recent review reported that the worldwide incidence of juvenile arthritis ranges from 0.8 to22.6 per 100,000 children per year and the prevalence ranges from 7 to 401 per 100,000children. The wide range between the lowest and highest estimates of incidence and

prevalence is a result of differences in study design and methods (Gare 1999; Manners andBower 2002). Geography and ethnicity are also potential contributors to differences in thefrequency of juvenile arthritis (Petty 2003). A comparison of methodologically similarEuropean and American studies showed that the annual incidence of juvenile arthritis rangesfrom 5 to 18 per 100,000 and the prevalence ranges from 30 to 150 per 100,000 children

under 16 years of age (Gare 1998).

5.2 Burden of disease

Worldwide, rheumatoid arthritis affects approximately 1% of the population and up to3% of people over 65 years of age (Massardo et al 2002). The disease is associatedwith a high total cost. The annual direct cost of rheumatoid arthritis in the UnitedStates is estimated to be US$4.2 billion (Russak et al 2003) and indirect costs are

estimated to be two to three times this amount. The majority of the indirect cost isrelated to the high prevalence of work disability among people with rheumatoidarthritis (Yelin 2003).

Incidence

According to a recent World Health Organization report (WHO 2003), the global incidence ofrheumatoid arthritis ranges from 20 to 300 cases per 100,000 people per year. Data from arange of American and European sources indicate that the incidence of rheumatoid arthritis ishigher among women than men (Silman and Hochberg 2001). There is evidence that the

incidence of rheumatoid arthritis is slowly declining over time, particularly among women(MacGregor and Silman 2003; Gabriel 2001).

Prevalence

Rheumatoid arthritis affects approximately 0.5% to 1.6% of the population in developedcountries (Kvien and Uhlig 2004; Lawrence et al 1998). Prevalence figures vary depending onthe source of information and the method of classifying rheumatoid arthritis. Surveysinvolving self-report of the condition generally produce higher prevalence rates than

prevalence data from registries or clinical examination, although the pattern of distribution interms of age and gender is similar.

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Clinical, radiological, serological prevalence

The prevalence of rheumatoid arthritis is 5 per 1000 males and 10 per 1000 females on thebasis of data obtained from clinical examination and diagnosis (Cunningham and Kelsey

1984). On the basis of radiological changes coupled with rheumatoid-factor positivity,rheumatoid arthritis prevalence figures are 7 per 1000 males and 16 per 1000 females. Usingserological results alone, the prevalence of rheumatoid arthritis among males is 3 per 1000,and 7 per 1000 among females (Mikkelsen et al 1967).

Self-reported prevalence

Population-based surveys of rheumatoid arthritis prevalence have yielded a range of results.In the 2001 National Health Survey, 438,200 Australians self-reported physician-diagnosedrheumatoid arthritis, or approximately 2.3% of the population. Nearly 60% of the reports werefrom women (ABS 2002a). In a South Australian survey, 3.2% of men and 4.9% of women

self-reported rheumatoid arthritis (Hill et al 1999).

Overseas studies show that self-reported prevalence of rheumatoid arthritis is highercompared to clinical diagnosis of the condition, although the pattern of prevalence amongmen and women is generally similar (Picavet and Hazes 2003). In studies conducted on thegeneral population, including groups of older women, between 12% and 22% of people inthese studies had correctly self-reported rheumatoid arthritis when compared to the clinicalfindings (Kvien et al 1996; Gram et al 1997; Star et al 1996; Ling et al 2000). In a studyconducted on people attending a rheumatology clinic, the proportion of people with an exactmatch between self-reported and clinical findings was much higher, at 90% (Rasooly et al1995). Accuracy of self-report of rheumatoid arthritis is enhanced when the question includesa report of care by a physician (Ling et al 2000; Kvien et al 1996).

The misunderstanding and misuse of the term rheumatoid arthritis, and terms to describerheumatic diseases in general, is one reason why the prevalence of rheumatoid arthritis ishigher when self-reported compared to findings on clinical examination (Gram et al 1997).Other issues include the way in which the survey question is posed and what type ofinformation is requested, and whether there is a distinction made between the different formsof arthritis (Picavet and Hazes 2003). In addition, willingness to report, recall ability,understanding of explanations and terms used by health professionals, and perceived impacton quality of life are general issues that can affect self-reporting.

Health services utilisation

Health services utilisation is greater among people with rheumatoid arthritis compared to non-arthritic people with similar demographic, economic and co-morbidity profiles (Dunlop et al2003; Girard et al 2002). The duration of the disease and its related impairment create a needfor ongoing contact with the health system.

Studies conducted overseas have revealed gender differences in the utilisation of healthservices by people with rheumatoid arthritis. There are more delays in referring women withearly rheumatoid arthritis to specialist care compared to men (Lard et al 2001), and despite ahigher prevalence of the condition, women undergo fewer joint replacement procedurescompared to men (Hawker et al 2000). In general, utilisation of health services is inversely

related to socio-economic status (Badley 2001). An Australian study shows that women witharthritis have lower socio-economic status than men (Hill et al 1999).

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While most people with rheumatoid arthritis are managed in the community, between 10%and 26% of people are hospitalised every year (Cooper 2000; Yelin and Wanke 1999). Themajority of hospitalisations associated with rheumatoid arthritis involve joint replacementsurgery (Yelin and Wanke 1999). Data from the Australian Orthopaedic Association National

Joint Replacement Registry show that rheumatoid arthritis is a principal diagnosis in 1.8% ofprimary total hip and 2.5% of primary total knee replacement procedures and is the secondmost common reason for primary total knee replacement surgery after osteoarthritis (AOA2003).

Over the past four years, there has been a downward trend in the proportion of total hip andknee joint replacement procedures associated with a diagnosis of rheumatoid arthritis despitean increase in the overall number of joint replacement procedures over that period (AOA2003). This trend has been reported elsewhere; patients diagnosed with rheumatoid arthritisafter 1985 are less likely to undergo joint replacement surgery. This may reflectimprovements in disease management, a change in the nature of the disease or changes inorthopaedic and rheumatoid practice (da Silva et al 2003; Lubeck 2003).

Costs

Costs to society

Most of the studies on the cost of rheumatoid arthritis have been conducted in North Americaand Europe. Overseas data show that the total (direct plus indirect) cost of rheumatoidarthritis to society is substantial. In Canada, the total cost of rheumatoid arthritis iscomparable to that of cancer, and in the United States it is similar to the costs of coronaryartery disease and cancer (Badley 1995). Cost predictors in overseas studies include poorer

functional status, female gender, the presence of co-morbid conditions and socio-demographiccharacteristics. Higher income and education levels are associated with higher drug costs andlower hospitalisation costs (Yelin and Wanke 1999; Leardini et al 2002; Michaud et al 2003).

The majority of the cost associated with rheumatoid arthritis is the indirect cost associatedwith work disability, which increases with disease duration. The average annual indirect costis US$9,700 (Yelin 2003). Over a lifetime, work disability costs range from US$225,000 toUS$370,000 per affected individual (Wong et al 2001). The direct costs of rheumatoidarthritis amount to an average of US$5,400 per affected individual per year (Yelin 2003) andare estimated to range from US$65,000 to more than US$130,000 (1998 dollars) per affectedindividual over the course of a lifetime (Wong et al 2001; Gabriel et al 1999b).

In Australia, the direct cost of rheumatoid arthritis to the health system was estimated to beA$129 million in 1993-94 (Mathers and Penm 1999). In 2000-01, the direct cost ofrheumatoid arthritis was estimated to be A$249 million, or 0.51% of the total allocated healthsystem expenditure, based on data sources used in the preparation of a recent report (AIHW2004). The direct costs in these studies included public and private hospital costs, togetherwith nursing home, medical, pharmaceutical and diagnostic testing costs.

Another Australian study, using different costing methodology, measured direct as well asindirect costs. The total cost of both rheumatoid arthritis and osteoarthritis was estimated to

be A$8.96 billion dollars in 1999-00, with three quarters of this amount attributed to indirectcosts. The total cost per capita was A$468.93. Separate cost data for rheumatoid arthritis werenot available in the study (Access Economics 2001b).

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Costs to individuals

People with rheumatoid arthritis in the community have three times the direct medical costs oftheir age and sex matched non-arthritic counterparts (Felts and Yelin 1989). Costs are related

to the management of the condition and co-morbidities. People with rheumatoid arthritis incursignificantly higher direct costs associated with in-hospital care and medication, imaging andother diagnostic tests, medical services and equipment compared to unaffected individuals(Gabriel et al 1997).

In Australia, the average out-of-pocket amount per annum is A$1,513 for individuals withrheumatoid arthritis. Costs increase with the duration of disease and include items such as co-

payment for prescription and purchase of non-prescription medications, assistive devices,laboratory and imaging tests, and visits to health professionals. Expenses are higher forwomen than men and younger people with private health insurance incur higher out-of-pocketcosts than older people with pension support. Poorer general health status is associated withhigher out-of-pocket costs (Lapsley et al 2002).

Trends

Direct and indirect costs associated with rheumatoid arthritis are likely to rise in bothdeveloped and developing countries. Currently, the majority of the cost to society isassociated with hospitalisation for joint replacement surgery, although there is a downwardtrend for this procedure. There is evidence that the advent of biological and other

pharmaceutical agents is increasing the direct cost of rheumatoid arthritis. In addition, asmore women attain higher wages in the labour market, the costs associated with workdisability and lost income will increase (Yelin 2003).

5.3 Impact

Health-related quality of life

Rheumatoid arthritis has a substantial impact on health-related quality of life owing to itspainful and disabling nature (Rupp et al 2004). An Australian study demonstrated thatrheumatoid arthritis has a significant impact on pain, physical function, social and emotionalfunction, and mental health (Hill et al 1999).

Pain

Pain is the major area of concern for people with rheumatoid arthritis (van Riel et al 2003;Minnock et al 2003b). Pain is identified as the preferred area for improvement by almost 70%of affected individuals, including those with low pain scores. Preference for improved painmanagement is associated with lower age, higher pain levels and lower self-efficacy scores(Heiberg and Kvien 2002). Twenty percent of people with rheumatoid arthritis report high

pain levels despite a lack of objective measures (Thompson and Carr 1997).

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Disability

Arthritis (all forms) is the leading cause of disability in Australia (AIHW 2002b). Thecondition involves a progressive loss of independence as activities of daily living becomemore difficult to perform. Disability in rheumatoid arthritis is associated with the extent of

joint damage, and influenced by factors such as age, female gender, low socio-economicstatus, income and educational level, and pain and depression (Scott 2000). The effects ofdisability have a substantial impact on individuals and their roles, and on their families.Disability influences psychosocial function and can lead to anxiety, depression and fatigue(Kvien 2004).

Disability associated with rheumatoid arthritis also has a substantial economic impact. Workdisability starts early in the course of rheumatoid arthritis as a result of functional impairmentand fatigue. Approximately 20% to 30% of people become work disabled within the first twoto three years of the disease (Sokka 2003), and after five years the incidence of workdisability ranges from nearly 30% to 50% among those previously in paid employment(Young et al 2002). Between 22% and 40% cease employment after five years (Young et al

2002; Sokka et al 1999), and within ten years at least 50% of affected individuals are unableto continue with full-time employment (Brooks 1997).

Job loss occurs earlier among people involved in manual work compared to those in sedentaryoccupations. Risk factors for work disability are manual work and a high baseline level ofdisability. In addition, severity of disease, older age of disease onset, female gender and lowereducational level are predictive of early occupational disability in nearly 80% of cases(Young et al 2002). Interventions such as occupational counselling, career planning andretraining should be considered early in the course of the disease to lessen the substantialeconomic impact of rheumatoid arthritis-related work disability on individuals and society.

Psychosocial impact

The pervasive nature of arthritis symptoms and their effect on physical, social andoccupational activities can be discouraging, resulting in psychological sequelae such asanxiety, depression and helplessness (Keefe and Bonk 1999). Between 20% and 25% of

people with severely disabling rheumatoid arthritis are affected by anxiety and depression(Dickens et al 2003), a higher rate than found in the general population (Hill et al 1999).Depression care, social support and self-efficacy are associated with improved healthoutcomes (Brekke et al 2003).

There is correlation between psychosocial factors and levels of self-reported pain anddisability in people with rheumatoid arthritis (Brekke et al 2003). Improvement in depression

care reduces pain and improves functional status and quality of life in people with arthritis(Lin et al 2003).

The perception of adequate positive social support, including support from family and friendsand the knowledge level of the primary caregiver, can improve overall health outcomes(Minnock et al 2003a). People with adequate social support and without independent socialstress are more likely to respond to assistance with coping and help with managing thedisability associated with rheumatoid arthritis (Dickens et al 2003).

Self-efficacy, which is related to the concepts of self-esteem and locus of control and refers tothe capacity to self-manage symptoms, is associated with lower levels of depression(Symmons 2003). Changes in self-efficacy are positively associated with changes in

perceived health status among people with rheumatoid arthritis (Brekke et al 2003).

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Mortality

Survival is significantly lower among individuals with rheumatoid arthritis compared to thegeneral population, reduced by an average of 5 to 10 years (Kvien 2004). Cardiovascular

disease and infection are the leading causes of death in rheumatoid arthritis (Gabriel et al2003).

There were 135 deaths in Australia attributed to rheumatoid arthritis in 1998 (AIHW 2002a),although it is not known how many individuals with rheumatoid arthritis died of other causessuch as co-morbid conditions.

5.4 Risk factors and determinants of health

Overview

Rheumatoid arthritis is believed to be associated with a family history of the disease andexposure to an environmental trigger, although the exact cause is unknown. A number of riskfactors and determinants may contribute to the development and/or progression of rheumatoidarthritis. Further epidemiological research is required to improve knowledge of the riskfactors and health determinants associated with the condition.

Description of risk factors and determinants

Age

The incidence and prevalence of rheumatoid arthritis increase with age. Globally, the peakincidence of rheumatoid arthritis occurs between the ages of 55 and 64 years in women and65-75 years in men and the age of onset is rising (Symmons 2002). The prevalence ofrheumatoid arthritis increases with age and starts to decline at approximately 70 years of age(Linos et al 1980; Picavet and Hazes 2003).

In addition to being a risk factor for the onset of rheumatoid arthritis, older-age onset of thecondition is characterised by more rapid functional decline than younger-age onset (Symmons2002).

Gender

Rheumatoid arthritis is more common among women than men, however, the ratio of femaleto male cases decreases with age (Kvien 2004). Female gender may have an impact onsymptoms and functional outcome (Symmons 2002). The reason for the higher incidence and

prevalence among women has not been established (Kvien 2004).

Family history

The familial nature of rheumatoid arthritis suggests that genetic risk factors play a role in

susceptibility to rheumatoid arthritis (Gabriel 2001). Based on twin studies, the genetic

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contribution to rheumatoid arthritis susceptibility is estimated to be 60% (MacGregor et al2000). Genetic variation in the human leukocyte antigen region is a contributing factor to thegenetic risk of rheumatoid arthritis (Stastny 1978).

Smoking

A number of cohort and case-control studies have shown that cigarette smoking is associatedwith an increased risk of rheumatoid arthritis (Silman and Pearson 2002; Stolt et al 2003;Wilson and Goldsmith 1999; Hutchinson and Moots 2001). Many of these studies havedemonstrated an association only for seropositive rheumatoid arthritis. Smoking is associatedwith the production of rheumatoid factor (Uhlig et al 1999), and smokers are more likely toexhibit extra-articular features such as rheumatoid vasculitis, nodules and lung disease(Symmons 2003). The increased risk from smoking is related to duration rather than intensityof smoking, and may remain for several years after smoking cessation (Stolt et al 2003).

Alcohol consumption

Moderate consumption of alcohol has been shown to protect against the development ofrheumatoid arthritis in women (Ollier et al 2001), although other reports demonstrate noassociation between alcohol consumption and the risk of rheumatoid arthritis (Cerhan et al2002).

Obesity

There is conflicting evidence as to whether obesity is a risk factor for the development ofrheumatoid arthritis (Symmons et al 1997; Hernandez-Avila et al 1990).

Immune function

Immune response may play a role in the development of rheumatoid arthritis. Autoimmunediseases, such as Type I diabetes and thyroid disease, occur more frequently in people withrheumatoid arthritis compared to those without the condition. There is some evidence that

previous blood transfusion increases the risk of rheumatoid arthritis onset (Symmons et al1997).

Infectious agents

An infectious cause for rheumatoid arthritis has been suggested, although there is noepidemiological or serological evidence of such a link. There are conflicting reports that

Epstein-Barr virus and human parvovirus B19 are associated with the risk of rheumatoidarthritis. Other infectious agents, including cytomegalovirus, retroviruses and mycobacteriahave also been proposed as infectious triggers; however, there is no conclusive evidence of anassociation and no single organism identified (MacGregor and Silman 2003; Ollier et al2001).

Caffeine consumption

Longitudinal data have linked coffee consumption with seropositive rheumatoid arthritis(Heliovaara et al 2000), although a more recent study found no evidence of an association

between coffee, decaffeinated coffee, or tea consumption and the onset of rheumatoid arthritis

(Karlson et al 2003a).

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Co-morbid conditions

As treatment for rheumatoid arthritis becomes more effective, people with the condition areliving longer and the impact of co-morbid conditions on disability and mortality is becomingmore apparent (Wasko 2004). Rheumatoid arthritis is highly predictive for a rise in future co-

morbidities after controlling for baseline co-morbidity (Gabriel et al 1999a).

Co-morbid conditions have been reported in between 27% and 33% of people withrheumatoid arthritis, with no apparent gender differences (Kroot et al 2001; Hallert et al2003). Cardiovascular conditions are the most frequently reported coexisting conditions(Kroot et al 2001), and cardiovascular disease is the most common cause of premature deathin people with rheumatoid arthritis (Gordon et al 2002). Compared to people without thecondition, people with rheumatoid arthritis are at greater risk of developing congestive heartfailure, dementia, chronic obstructive airways disease and peptic ulcer disease (Gabriel et al1999a).

There is evidence that co-morbid conditions are overlooked in people with rheumatoid

arthritis and that health maintenance and preventative care services are less than optimal(Kremers et al 2003).

Psychosocial factors

There is correlation between psychosocial factors and the level of self-reported pain anddisability in people with rheumatoid arthritis. There is a higher rate of anxiety and depressionamong people with rheumatoid arthritis, particularly those with severe disability (Dickens etal 2003), than the general population (Hill et al 1999). While depression is associated withhigher disability, there is no evidence of an association with the development or the

progression of the condition (Symmons 2003).

Environmental factors

Rheumatoid arthritis is rare in undeveloped and rural areas (Symmons 2002), and theincidence of rheumatoid arthritis is higher among groups residing in urban areas. As a result,urbanisation and air quality have been proposed as risk factors for the condition (Bankhead etal 1996; Solomon et al 1975), although reports of such an association are conflicting(MacGregor et al 1994; Lau et al 1993).

Oestrogens

The incidence of rheumatoid arthritis among women is highest in the peri-menopausalperiod indicating that female sex hormones may play a role (Kuiper et al 2001). Thereis evidence that pregnancy influences the timing of the onset of rheumatoid arthritis,which is lower during pregnancy but higher in the first year post-partum (Silman et al1992; Symmons 2003). Pregnancy is not believed to have a protective influenceoverall (MacGregor and Silman 2003). There is conflicting evidence about theinfluence of oral contraceptives or hormone replacement therapy on the risk ofrheumatoid arthritis (Symmons 2002; MacGregor and Silman 2003).

Nutritional factors

The frequency and severity of rheumatoid arthritis is lower in regions where the diet is rich inomega-3 fatty acids (Symmons 2003). It has therefore been suggested that a diet rich in olive

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oil, oil-rich fish, fruit and vegetables may protect against the development of rheumatoidarthritis, although few studies have been conducted (Pattison 2004a).

Eating fish or fish oils may provide protection from cardiovascular disease, the most commoncondition coexisting with rheumatoid arthritis (Kroot et al 2001). Supplementation with fish

oils has been associated with the relief of symptoms of established rheumatoid arthritis in anumber of studies (Ariza-Ariza et al 1998; Pattison et al 2004b).

Treatment with disease-modifying drugs

Access to early treatment with disease-modifying anti-rheumatic medication is the greatestdeterminant of health outcomes in rheumatoid arthritis. There is substantial evidence thatdisease-modifying anti-rheumatic drugs reduce radiological progression, reduce functionaldisability and may improve life expectancy particularly when commenced early in the courseof the disease (Symmons 2002) (refer to Section 5.8).

Socio-economic factors

There are conflicting reports that socio-economic level is associated with the development ofrheumatoid arthritis, however, the condition is more prevalent among lower socio-economicgroups (Jacobi et al 2003). Low socio-economic status has been linked with the progressionof the disease (Symmons 2003; Bankhead et al 1996).

There are conflicting reports as to whether formal education is associated with the incidenceand prevalence of rheumatoid arthritis (Vliet Vlieland et al 1994; Gordon and Hastings 2003).An Australian study demonstrated that the prevalence of rheumatoid arthritis was lowestamong those who attended university and highest among those leaving school before 15 yearsof age (Hill et al 1999).

An association between type of occupation and the risk of developing rheumatoid arthritis hasnot been confirmed. There is some evidence of an association between organic dust exposureand the incidence of rheumatoid arthritis in men (Olsson et al 2004).

AREA FOR URGENT ACTION: Reduce disadvantage by considering groups withspecial needs

Potentially modifiable risk factors and determinants

Table 5.1 outlines the potentially modifiable and the non-modifiable risk factors and healthdeterminants that are associated with the development and/or progression of rheumatoidarthritis, as described in the preceding text.

Table 5.1: Risk factors and determinants of health for rheumatoid arthritisRisk Factors Potentially Modifiable Non-modifiableBehavioural factors x Smoking -

Psychosocial factors x Depression -

Biological risk factors x Co-morbid conditions x Family history

x Female gender

x Older age

x Immune response

Environmental risk factors x Early treatment with disease-

modifying anti-rheumatic drugs

x Socioeconomic status

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5.5 Non-pharmacological interventions for rheumatoid arthritis

Due to the scope of this report, a systematic review of all non-pharmacological interventionsfor rheumatoid arthritis was not conducted. A summary of Cochrane Reviews in Table 5.2

provides Level I evidence (Appendix C) on non-pharmacological interventions forrheumatoid arthritis.

In general, few studies have been conducted and many have methodological limitations.Insufficiency of evidence should not be construed as evidence of ineffectiveness, or used as a

basis for the non-provision of a treatment, but rather as an indication of the need for furtherresearch.

Table 5.2: Cochrane Reviews of non-pharmacological interventions for rheumatoidarthritis

Cochrane Review Population and OutcomeMeasures

Conclusion

Transcutaneouselectrical nervestimulation (TENS)Brosseau et al 2004d(last updated 2003)

Adults with hand rheumatoidarthritisPain (grip, resting), OMERACT1993 outcome measures

Acupuncture-like TENS (AL-TENS) has astatistically and clinically beneficial effect onpain and a clinical benefit on muscle powerover placebo. There was no clinical benefitfrom conventional TENS (C-TENS) on pain vsplacebo; however, C-TENS resulted in a clinicalbenefit on patient assessment of change indisease over AL-TENS.

Electrical stimulationPelland et al 2004 (lastupdated 2002)

Adults with hand rheumatoidarthritisHand function

Limited evidence on which to draw conclusionsas only one study met inclusion criteria.

Balneotherapy (spatherapy)Verhagen et al 2004(last updated 2003)

Diagnosis of rheumatoid arthritisWHO/ILAR core set of endpoints

Insufficient evidence to support claims ofpositive findings in most studies due to poormethodological quality, absence of adequatestatistical analysis and health-related quality oflife outcome measures.

Therapeutic ultrasoundCasimiro et al 2004a(last updated 2002)

Adults with diagnosis ofrheumatoid arthritisPain, OMERACT 1993 outcomemeasures

Therapeutic ultrasound in combination withexercises, faradic current and wax baths is notsupported. Therapeutic ultrasound alone to thedorsal (top) aspect and palm of the handsignificantly increased grip strength and wristdorsal flexion and reduced morning stiffnessand the number of swollen and painful joints.Conclusion based on results of one small studywith methodological limitations and smallsample size.

ThermotherapyRobinson et al 2004(last updated 2001)

Adults with diagnosis ofrheumatoid arthritis, excludingaxial jointsPain, OMERACT 1993 outcomemeasures

No significant effect of heat or ice packapplication, cryotherapy or faradic baths onobjective measures of disease activity. Nosignificant differences between wax vstherapeutic ultrasound or faradic bath vsultrasound. The benefits of thermotherapy used

as palliative therapy or adjunct therapycombined with exercises are unclear. Noadverse effects are reported.

Splints and orthosesEgan et al 2004(last updated 2002)

Adults with rheumatoid arthritis,including mixed populations if>50% with rheumatoid arthritisOMERACT 1993 outcomemeasures

Insufficient evidence to draw conclusions,however working wrist splints and resting wristand hand splints do not have adverse effects,are low cost and may provide pain relief forsome people. Extra-depth shoes, with orwithout insoles, may relieve pain on walkingand weight-bearing. Supported insoles do notdecrease pain or improve function but may limitprogression of hallux valgus angle.

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Conclusion

Dynamic exercisetherapyVan den Ende et al2004

(last updated 2000)

Diagnosis of rheumatoid arthritisAerobic capacity, muscle strength,joint mobility, functionalperformance, pain, disease activity

Dynamic exercise therapy has a positive effecton physical capacity (increased aerobiccapacity and muscle strength). No detrimentaleffects on disease activity and pain were

observed. The effects of dynamic exercisetherapy on functional ability and radiologicalprogression are unclear.

Low level laser therapy(Classes I, II and III)Brosseau et al 2004e(last updated 2001)

Adults with diagnosed rheumatoidarthritisOMERACT 1993 outcomemeasures, additionalphysiotherapy outcomes

Insufficient data to draw firm conclusions, butevidence suggests that low level laser therapyrelieves pain. Data are lacking on differentaspects of treatment procedures. No sideeffects were reported.

Patient educationRiemsma et al 2004(last updated 2003)

Adults with diagnosed rheumatoidarthritisOMERACT 1993 outcomemeasures

Patient education has a small significant effecton disability, joint counts, patient globalassessment, psychological status anddepression. The clinical effects are difficult todetermine because education is alwaysprovided in addition to usual care.

Pre-operativeeducation vs standard

care for hip or kneereplacementMcDonald et al 2004(last updated 2003)

All patients undergoing plannedtotal hip or total knee replacement

(including osteoarthritis andrheumatoid arthritis).Postoperative pain, length ofhospital stay, compliance, patientsatisfaction, deep vein thrombosis,range of motion, anxiety, mobility

Insufficient evidence to support the use of pre-operative education for people undergoing hip

or knee replacement surgery in relation tomeasures of pain, function and length of stay.Has modest beneficial effect on anxiety.

Herbal therapyLittle and Parsons 2004(last updated 2000)

Diagnosis of rheumatoid arthritisClinical (pain, mobility, gripstrength, use of non-steroidal anti-inflammatory drugs) and non-clinical (serum lipids, fatty acids)measures of efficacy

Single studies of gamma-linolenic acid (eg.evening primrose oil, borage seed oil, blackcurrant seed oil) are insufficient to determineefficacy.

Acupuncture andelectroacupunctureCasimiro et al 2004b(last updated 2002)

Adults with diagnosed rheumatoidarthritisPain, OMERACT 1993 outcomemeasures

Insufficient evidence to support acupuncture orelectroacupuncture due to methodologicallimitations including the small sample size ofthe one included study.

Occupational therapySteultjens et al 2004(last updated 2003)

Diagnosis of rheumatoid arthritisPain, fatigue, function,independence, health-relatedquality of life

Strong evidence of efficacy for instruction onjoint protection on functional ability, andpositive effect from comprehensiveoccupational therapy.

5.6 Pharmacological interventions for rheumatoid arthritis

Due to the scope of this report, a systematic review of all pharmacological interventions forrheumatoid arthritis was not conducted. A summary of Cochrane Reviews in Table 5.3

provides Level I evidence (Appendix C) of pharmacological interventions for rheumatoid

arthritis.

Table 5.3: Cochrane Reviews of pharmacological interventions for rheumatoid arthritisCochrane Review Population and Outcome

MeasuresConclusion

Folic acid and folinicacid for reducing sideeffects of methotrexateOrtiz et al 2004 (lastupdated 1999)

x Diagnosis of rheumatoidarthritis (adults)

x Gastro-intestinal toxicity,beneficial effects ofmethotrexate

Low dose folate supplementation reduces themucosal and gastrointestinal side effects ofmethotrexate.

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Conclusion

Methotrexate vsplaceboSuarez-Almazor et al2004a

(last updated 1997)

x Rheumatoid arthritis of severeand long duration; highprevalence of positiverheumatoid factor and

previously failed other secondline disease-modifying anti-rheumatic drug therapy.

x Efficacy according toOMERACT 1993 measures

Statistically and clinically significant benefit(joint counts, pain and global and functionalassessments but not erythrocyte sedimentationrate) after 12 weeks methotrexate use. Highdrop out rate due to adverse effects ofmethotrexate.

Sulfasalazine vsplaceboSuarez-Almazor et al2004b(last updated 1997)

x Diagnosis of rheumatoidarthritis


Statistically and clinically significant benefit ondisease activity after short-term (6 months) use.

Injectable gold vsplaceboClark et al 2004(last updated 2000)



Clinically and statistically significant benefits.Useful for short-term treatment of rheumatoidarthritis, reducing joint swelling and erythrocytesedimentation rate. High drop out rate due totoxicity.

Auranofin (oral gold)

versus placeboSuarez-Almazor et al2004c(last updated 2000)

x Adults with rheumatoid arthritisreceiving no disease-modifyinganti-rheumatic drugs other thanauranofin


Small but clinically and statistically significant

benefit on disease activity following short-termuse (6 months).

Azathioprine vsplaceboSuarez-Almazor et al2004d(last updated 2000)



Statistically significant benefit on diseaseactivity in joints however insufficient data to testeffects on long-term functional status andradiological progression.

Leflunomide vsplacebo and vs otherdisease-modifyinganti-rheumatic drugsOsiri M et al 2004b

(last updated 2002)

x Adults meeting the ACR 1987criteria for rheumatoid arthritis,with active disease

x ACR core set of outcomemeasures for rheumatoid

arthritis.

Leflunomide improves all clinical outcomes anddelays radiologic progression at 6 and 12months vs placebo. Efficacy and adverseevents at 2 years of treatment are comparableto sulfasalazine and methotrexate.

Cyclosporine vsplaceboWells G et al 2004(last updated 2000)


x OMERACT 1993 outcomemeasures, toxicity

Cyclosporine has clinically and statisticallysignificant benefits in the short-term (up to oneyear) treatment of progressive rheumatoidarthritis. Toxicity is greater than placebo.

Antimalarials vsplaceboSuarez-Almazor et al2004e(last updated 2000)



Statistically significant benefits in pain, globalassessments, joint counts and erythrocytesedimentation rate. Overall effect appears to bemoderate. Low toxicity profile should beconsidered.

D-penicillamine vsplaceboSuarez-Almazor et al2004f(last updated 2000)



Clinically and statistically significant benefitscompared to placebo for pain, tender jointcounts, physician global assessment anderythrocyte sedimentation rate. The efficacy ofD-penicillamine is similar to other disease-

modifying anti-inflammatory drugs, but toxicityis higher.

Cyclophosphamide vsplaceboSuarez-Almazor et al2004g(last updated 2000)



Clinically and statistically significant benefitscompared to placebo for joint swelling andtenderness. Efficacy is similar to some disease-modifying anti-rheumatic drugs, but lower thanmethotrexate. Serious toxicity profile.

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Conclusion

Short-term, low-dosecorticosteroids vsplacebo and non-steroidal anti-

inflammatory drugs(NSAIDs)Gotzsche and Johansen(last updated 2003)

Diagnosis of rheumatoid arthritisJoint tenderness, grip strength,pain

Clinically and statistically significant benefitscompared to placebo and non-steroidal anti-inflammatory drugs.

Moderate-term, low-dose corticosteroids vsplacebo or controlCriswell et al 2004(last updated 1998)

Diagnosis of rheumatoid arthritisRequired reporting of jointtenderness, swelling, grip strengthand erythrocyte sedimentationrate; OMERACT 1993 outcomemeasures

Six-month prednisone treatment appears to besuperior to placebo and comparable totreatment with aspirin or chloroquine.

Infliximab vs placeboand vs controlBlumenauer et al 2004b(last updated 2002)

Adults meeting the ACR 1987criteria for rheumatoid arthritis,with active diseaseResponse according to WHO,ILAR core set of disease activitymeasures and ACR rheumatoid

arthritis outcome measures

Infliximab (vs placebo; + methotrexate vsmethotrexate) reduces rheumatoid arthritisdisease activity. Based on two studies.

Etanercept vs placeboand vs controlBlumenauer et al 2004a(last updated 2003)

Adults meeting the ACR 1987criteria for rheumatoid arthritis,with active diseaseResponse according to WHO,ILAR core set of disease activitymeasures and ACR rheumatoidarthritis outcome measures

Etanercept (vs placebo; vs methotrexate;+methotrexate vs methotrexate) twice weeklygave statistically and clinically significant ACR20, 50 and 70 response rates and slowed jointdamage at 12 months.

Paracetamol vs non-steroidal anti-inflammatory drugWienecke andGotzsche 2004 (lastupdated 2003)

Diagnosis of rheumatoid arthritisPain

It is unclear whether non-steroidal anti-inflammatory drugs (NSAIDs) have any morethan a pain relieving effect in rheumatoidarthritis (and other musculoskeletal disorders).It is unclear whether the trade offs in benefitsand harms of NSAIDs are preferable to those ofparacetamol.

Rofecoxib vs placebo

and vs controlGarner et al 2004a(last updated 2002)

Diagnosis of rheumatoid arthritis

OMERACT 1993 outcomemeasures, ACR 20 response,toxicity

Rofecoxib 25 and 50mg produced statistically

significant benefits compared to placebo with asimilar safety profile. Rofecoxib 50mg/day*demonstrated similar efficacy to naproxen500mg twice a day with lower incidence ofgastrointestinal adverse events but isassociated with cardiovascular complications.

(* A dose of 50mg/day is twice the maximumlicensed daily dose of rofecoxib for rheumatoidarthritis in Australia)

Celecoxib vs placeboand controlGarner et al 2004b(last updated 2002)

Diagnosis of rheumatoid arthritis(and osteoarthritis) populationsincluded; combined data not used)OMERACT 1993 outcomes, ACR20 response, toxicity

Efficacy of celecoxib equivalent to naproxenand diclofenac. Significantly greaterimprovement in ACR 20 criteria compared toplacebo. No evidence on relative safety profilesof celecoxib and standard non-steroidal anti-inflammatory drugs combined with gastro-

protective agents.

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5.7 Clinical practice guidelines for rheumatoid arthritis

The American College of Rheumatology (ACR 2002) and the Scottish IntercollegiateGuidelines Network (SIGN 2000) have published clinical practice guidelines for the

management of rheumatoid arthritis. The SIGN guidelines were developed to inform themanagement of early rheumatoid arthritis, which precludes mention of particular drug agents.Although the target audiences differ, the recommendations in both guidelines are compared inTable 5.4, and an evaluation of the guideline development methodology is provided in Table5.5.

Table 5.4: Rheumatoid arthritis practice guidelines: comparison of recommendationsGuideline

Intervention ACR SIGNMeasurement, diagnosis, monitoring

Establish RA diagnosis early -

Obtain baseline information and monitor progress using validateddisease specific and generic measures

-

Develop a treatment plan in consultation with the patient GPPDevelop a general health maintenance strategy, including routineprevention measures, assessment for and treatment of co-morbidities

-

Education and cognitive behavioural interventions GPP

Refer patients being considered for DMARDs to a rheumatologist -

Non-pharmacological interventions

Occupational therapy Dynamic exercises

ROM and strengthening exercise program

Resting and working splints - Podiatry referral - GPP

Inter-disciplinary team approach to care GPP

Systematic, regular evaluation of disease activity, adverse effects GPP

Early surgical intervention to optimise pre-operative functional status -

Pharmacological interventions

SSZ, MTX, IM gold, and penicillamine are equally effective DMARDs SSZ and MTX are the DMARDs of choice due to favourable efficacy andtoxicity profiles

-

MTX is recommended in cases of active disease or in the presence ofpoor prognostic indicators

Commence DMARDs within 3 months for any person with an establisheddiagnosis who has ongoing signs and symptoms of active disease

Sustain DMARD therapy in inflammatory disease to maintainsuppression

-

Combination DMARD therapy IE IE

NSAIDs (for those at risk of UGI adverse events: low dose prednisone,or nonacetylated salicylate, or a highly selective COX-2 inhibitor)

Administer gastr-oprotective agent with NSAID in aged with risk factorsfor PUB

** *

Use the lowest dose of NSAID compatible with pain relief - Reduce or withdraw NSAIDs when good response from DMARD is

achieved

-

Where possible, use simple analgesics in place of NSAIDs - GPP

Corticosteroids (low dose oral) Not for routineuse

Use the lowest possible dose of oral corticosteroids for the shortest timepossible; monitor for adverse effects

-

Intraarticular corticosteroids Use with caution

ACR=American College of Rheumatology (ACR 2002); SIGN=Scottish Intercollegiate Guidelines Network (SIGN 2000). E=excluded from thereview. GPP=recommended good practice point. PUB=perforation, ulcer, bleeding. *=65 years. **=75 years. - =no mention/discussion;IE=insufficient evidence to conclude; RA=rheumatoid arthritis; SSZ=sulfasalazine; UGI=upper gastrointestinal; DMARD=disease-modifyinganti-rheumatic drug; MTX=methotrexate; ROM=range of motion; IM=intramuscular; NSAID=non-steroidal anti-inflammatory drug

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Table 5.5: Rheumatoid arthritis practice guidelines: guideline development processaccording to AGREE (2001) criteria

Rating of guidelinesAGREE Domain ACR SIGNScope and purpose

1. Overall objective(s)

2. Clinical question(s)3. Target patient population

+

++

+

++

Stakeholder involvement

4. Development group representative5. Patient views and preferences

+-

++

Rigour of development

6. Systematic evidence search7. Selection of evidence explicit8. Formulation of recommendations explicit9. Benefits, side effects, and risks described10. Explicit link between evidence and recommendations11. External review12. Procedure for updating guideline

---+---

+++++++

Clarity and presentation

13. Specific and unambiguous recommendations14. Different treatment options

15. Key recommendations easily identified

++

-

++

+Applicability

16. End users of guideline stated17. Barriers to implementation are discussed18. Cost implications are discussed19. Tools for application20. Review/monitoring criteria defined21. Pilot testing

--+---

+++++-

Editorial independence

22. Editorial independence from funding body23. Conflicts of interest are stated

-+

++

+ indicates that the guideline has met the criterion; - indicates that it has not met the criterion; ACR=American College of Rheumatology (ACR2002); SIGN=Scottish Intercollegiate Guidelines Network (SIGN 2000). NB: This comparison was conducted by the author of this report.


5.8 Approaches to the management of rheumatoid arthritis

Early treatment with disease-modifying anti-rheumatic drugs

The efficacy of disease-modifying anti-rheumatic drugs in altering the clinical course andimproving the long-term outcome of rheumatoid arthritis is well documented. While initial

treatment of inflammation associated with rheumatoid arthritis usually involves the use ofnon-steroidal anti-inflammatory agents, these medications do not alter the course of thedisease or prevent damage to the joints. Disease-modifying anti-rheumatic drugs have beenshown to be effective compared to placebo in reducing inflammation, joint damage, pain andother primary outcome measures in people with rheumatoid arthritis and are most effectivewhen commenced early in the course of the disease. Despite the availability of effectivetreatment for rheumatoid arthritis, delays in diagnosing the condition and initiating disease-modifying treatment are not uncommon (Pincus et al 2002).

KEY OBJECTIVE: Promote early and optimal management of rheumatoid arthritis tominimise joint damage.

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Evidence review

There is strong evidence that significant joint damage occurs early in the course ofrheumatoid arthritis and early treatment with disease-modifying anti-rheumatic drugs is

beneficial (Quinn and Emery 2003; Cush 2003; Mullan and Bresnihan 2003). Early

introduction of disease-modifying medication can prevent irreversible joint damage (Emery1997; Epstein 2003). Delays of just a few months have an impact on long-term outcomes andon the potential for remission (Nell et al 2004). A few of the larger studies documenting theeffects of early use of disease modifying anti-rheumatic drugs are described here.

Data from the FIN-RACo Trial Group (Mottonen et al 1999), which demonstratedthat a combination of disease-modifying anti-rheumatic drug therapy and

prednisolone produces better outcomes in people with early rheumatoid arthritis thana single drug strategy, were later analysed to determine whether a delay in institutingdisease-modifying anti-rheumatic drugs therapy affected outcomes. Delayingintroduction of a single disease-modifying anti-rheumatic drug by four months ormore from the onset of symptoms reduced the rate of disease remission (Mottonen et

al 2002).

An observational inception study by Bukhari et al (2003) used paired x-rays obtainedat years one and five to determine whether disease-modifying anti-rheumatic drugtherapy provided a protective effect and whether the timing of treatment influencedthis effect. There was greater impact on disease outcome when treatment was initiatedwithin six months of disease onset, and early treatment reduced damage after fiveyears compared to delayed treatment.

The COBRA trial (Boers et al 1997) demonstrated that combination therapy wassuperior to the use of one disease-modifying agent alone in suppressing diseaseactivity and slowing radiological progression. A follow up study of subjects in the

COBRA trial showed that in order to sustain the suppression of radiologicprogression, disease-modifying therapy should be commenced early. The rate ofdisease progression is related to the amount of radiological damage, and hence, earlytreatment is essential to prevent or minimise damage at the outset (Landewe et al2002).

Verstappen et al (2003) compared the early use of disease-modifying anti-rheumaticdrugs to the use of non-steroidal anti-inflammatory drugs alone, and to administeringdisease-modifying anti-rheumatic drugs as the disease progressed. After one year,early treatment with disease-modifying anti-rheumatic drugs was of greater clinical

benefit.

Van der Heijde et al (1996) reported that early use of a disease-modifying anti-rheumatic drug produced clinically important improvements at six and 12 monthscompared to the use of non-steroidal anti-inflammatory drugs alone, and slowed the

progress of the disease.

The early use of disease-modifying anti-rheumatic drugs delays radiologicalprogression (Stenger et al 1998). After two years, patients commenced on disease-modifying drug therapy at the time of diagnosis had significantly less radiological

progression of the disease than those receiving a conventional stepwise approach tothe introduction of disease-modifying drug therapy. During the study, treatmentresponse was closely monitored and adjusted as needed.

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In a double-blind placebo-controlled trial, Borg et al (1988) concluded thatintroduction of treatment with a disease-modifying anti-rheumatic drug as soon as

possible after diagnosis significantly improved physical function after two yearscompared to a treatment delay of approximately eight months, when clinical

deterioration had become evident. Seventy-five patients from this study (55% of theoriginal sample) were subsequently followed up after five years. The early treatmentgroup had enjoyed significant improvement in all outcome variables (pain, functionaland disability indices, radiological damage and depression) whereas only pain hadimproved significantly in the delayed treatment group after five years. In addition,there was radiological evidence supporting early treatment (Egsmose et al 1995). Thisfinding has since been replicated (Tsakonas et al 2000).

The duration of disease appears to be linked to the magnitude of treatment response.An analysis of baseline and outcome data of all participants (1435 people) involved in14 randomised controlled trials found that longer duration of disease was related todecreasing response, both in treatment and placebo groups. There was a 53%

response rate to active treatment among those with rheumatoid arthritis for less thanone year, and a treatment response rate of 43% after one to two years of diseaseduration. Decreasing response was also associated with prior use of a disease-modifying anti-rheumatic drug, higher disease functional class, low disease activityand female gender (Anderson et al 2000).

Combination versus single drug therapy

Disease-modifying drugs may be used alone or in combination. Combinations of such drugshave been advocated because of their differing mechanisms of action. There is evidence thatcombination therapy is more effective at slowing radiological progression than use of a singledisease-modifying agent (Mullan and Bresnihan 2003). While further research is needed,results thus far demonstrate benefit from this approach (Gossec and Dougados 2003).

Fast-tracking diagnosis and treatment

The early stage of rheumatoid arthritis presents an important opportunity to alter the course ofthe condition. There appears to be a therapeutic window within the first few months of diseaseonset when patients are more likely to experience remission following the introduction ofdisease-modifying anti-rheumatic drug therapy (Nell et al 2004).

The introduction of disease-modifying agents minimises joint destruction and confers

sustained benefits. It is therefore important to identify and diagnose rheumatoid arthritis earlyso that appropriate disease-modifying treatment can be instituted. However, while the benefitsof early treatment of rheumatoid arthritis are recognised and effective treatments areavailable, overseas reports show that delays in diagnosis and treatment initiation are notuncommon (Chan et al 1994).

Early diagnosis of rheumatoid arthritis is hindered by a number of factors, including a lack ofearly onset condition-specific features, poor sensitivity and specificity of serological markers,and an absence of radiological evidence early in the course of the condition (Bresnihan 2002;Emery 2002). Some primary care practitioners may lack the ability to recognise, diagnose ormanage rheumatoid arthritis because of the low prevalence of the condition (ACR 2002).

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Specialised knowledge and assessment skills are needed to identify early rheumatoid arthritis(Pincus et al 2002) and early referral of patients with inflammatory arthritis to arheumatologist is recommended. Access to the services of skilled rheumatologists improvesthe speed to diagnosis and treatment (Palferman 2003). Primary care physician education has

been shown to improve early referral rates (Kim and Weisman 2000).

Once a referral to a rheumatologist is made, there may be a delay of up to severalmonths before the visit occurs (Pincus et al 2002). The declining number ofrheumatologists relative to the (increasing) prevalence of rheumatic diseases mayresult in waiting periods of several months before new patients are seen (Schumacheret al 2003; Irvine et al 1999). One study estimated that diagnosis and treatment aredelayed for two months in 20% of people presenting with symmetrical jointsymptoms and rheumatoid factor-positivity (Kim and Weisman 2000). Access to earlydiagnosis and treatment remains a problem and there is unmet need in this area (Cush2003; Aletaha and Smolen 2003). Delays by patients in seeking help for arthriticsymptoms are another factor postponing early diagnosis and access to early treatment

(Chan et al 1994; van der Horst-Bruinsma et al 1998).

A number of approaches have been suggested to reduce the delay to treatment, although somemay not be sustainable for logistic and economic reasons (Pincus et al 2002):

A strategy to prioritise urgent visits to rheumatologists; Telephone screening of new referrals; Early arthritis clinics; Strategies to address the shortage of rheumatologists; Use of physician extenders; Including the rheumatic diseases in the curricula of non-rheumatologist courses; Self-management/alternative programs for people with other chronic rheumatic

diseases to free up more time for patients with rheumatoid arthritis; Internet use to communicate with people with an exacerbation of their condition.

AREA FOR URGENT ACTION: Reduce disadvantage by considering groups withspecial needs

Early arthritis clinics

Early arthritis clinics have been developed to address the problems of access to

rheumatologists and to other services for people with rheumatoid arthritis by providing avisible service and point of referral. Such clinics have been shown to reduce the time lag

between symptom onset and the first consultation with a rheumatologist by at least threemonths (van der Horst-Bruinsma et al 1998; Emery 1994). In addition to faster referral,dedicated clinics have been shown to improve the speed and reliability of diagnosis (Irvine etal 1999; Chan et al 1994; Emery 1994; van der Horst Bruisnma et al 1998).

Early arthritis clinics also provide an important opportunity to collect longitudinal data onpeople with rheumatoid arthritis. Monitoring people with the condition over time providesvaluable information on disease impact, risk factors, ill-health and death, incidence and

prevalence, outcomes and predictors of outcome, and treatment effects (Symmons and Silman2003).

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Criteria for early referral

Another measure to improve the speed to diagnosis and treatment involves educating generalpractitioners to identify potential cases of rheumatoid arthritis and to initiate urgent referral toa rheumatologist. The following criteria can be used as a clinical guide to early referral for

general practitioners (Emery et al 2002):

More than three swollen joints; Metatarsophalangeal/metacarpophalangeal involvement (i.e. feet and toes, hands and

fingers); Morning stiffness lasting longer than 30 minutes.


Self-management of rheumatoid arthritis

The management of chronic conditions such as rheumatoid arthritis involves complex andlong-term partnerships between affected individuals and health professionals, and with other

people and organisations providing ongoing care and support. The majority of care isprovided in the community and in primary care settings (Rothman and Wagner 2003).

The affected individual and their carers are often expert in the day-to-day management of thecondition (von Korff et al 2002), therefore, helping them make daily decisions to manage thecondition is an important strategy (Riemsma et al 2004). By enhancing knowledge, skills andself-confidence (self-efficacy), education programs can inform and empower individuals toself-manage their health and participate in decisions about their care. Self-efficacy is relatedto the concepts of self-esteem and locus of control (Brekke et al 2003), and is a means ofclosing the gap between knowledge and behaviour in self-management (Rimal 2000).

There is an association between self-efficacy and pain (Lefebvre et al 1999), fatigue(Riemsma et al 1998a), depression (Smarr et al 1997), need for both informal and professionalcare (Riemsma et al 1998b), adherence to treatment regimes (Brus et al 1999), and overallhealth status in people with rheumatoid arthritis (Brekke et al 2001). Changes in self-efficacyare positively associated with changes in perceived health status among people withrheumatoid arthritis (Brekke et al 2003). Educational interventions that employ behaviouralmodification techniques coupled with disease-specific information can influence self-efficacy

(Lorig and Holman 1989). Such programs have been implemented in a number of countries,including Australia.

Education of people with rheumatoid arthritis is most effective when it incorporates abehavioural approach to the development of the skills and self-confidence required to self-manage. Education programs employing behavioural interventions have small but significanteffects on disability and depression, whereas programs focused solely on providinginformation do not demonstrate any significant effects or trends (Riemsma et al 2004).Education programs need to provide information in combination with problem-solving skillsand motivational activities (Dieppe and Brandt 2003).

Programs with an instructional component appear to have an effect on the health status of

individuals with rheumatoid arthritis. Significant effects on disability, joint count, patientglobal assessment, psychological status and depression outcomes have been demonstrated and

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there is a trend towards improved pain scores among people attending education programs;however, there are no significant effects on disease activity. There are conflicting reports overthe duration of the effect. One study reports that the beneficial effects are short-term(Riemsma et al 2004), and an Australian longitudinal study reports that reductions in pain andfatigue, and improvements in physical activity are sustained two years after attendance at an

arthritis self-management course (Osborne et al 2002).

Methodological limitations

Studies on the effectiveness of self-management education programs have methodologicallimitations. The mean quality score of studies included in the Cochrane Review by Riemsmaet al (2004) was low (3.26 out of a possible quality score of 8). Lack of description of therandomisation procedure, the inability to sufficiently blind participants and assessors, andlack of restriction of co-interventions were identified as the major methodological problems inthe included studies. Self-management is provided in addition to usual care, making itdifficult to distinguish between the effects of concurrent interventions. These limitations have

been similarly described in other systematic reviews on educational interventions (Riemsma

et al 2004).

A meta-analysis of controlled studies on the effects of self-management programs inrheumatoid arthritis (and osteoarthritis) found small beneficial effects on pain and disability.However, methodological standards in the included studies were unclear, drop out rates werehigh and there were differences in program delivery and intensity which made it difficult todraw firm conclusions (Warsi et al 2003).

Baseline self-efficacy, which is associated with educational level (Callahan et al 1996), has animpact on the success of self-management educational programs. There is evidence that

people with higher educational levels self-select to such programs which may partly explaintheir success (Brekke et al 2003). People with higher levels of education are more likely toself-manage (Katz 1998).

Despite limited evidence of an impact on objective measures, there is demand for self-management programs from people who wish to play an active role in their care. Education

programs can help individuals manage their day to day health needs and participate indecisions about their care.

KEY OBJECTIVE: Promote self-management to optimise health outcomes for peoplewith rheumatoid arthritis.

Early surgical intervention

Joint replacement surgery is often an inevitable consequence of the structural damage thatoccurs in rheumatoid arthritis. Over the course of the disease, approximately 25% of peoplerequire joint replacement surgery and between 25% and 50% require more than one suchreplacement (Palm et al 2002; Wolfe and Zwillich 1998). Improved surgical techniques and

products have improved the outcomes of joint replacement surgery and there is evidence thatfunctional and quality of life outcomes are better if surgery is performed earlier in the courseof the disease.

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The timing of surgical intervention appears to affect post-operative outcomes. There iscorrelation between pre-operative functional capacity and functional improvement following

joint replacement surgery. While severely disabled patients show improvement followingsurgery, patients who are less disabled prior to surgery have better functional outcomes(Jonsson and Larsson 1991). Postponing joint replacement surgery appears to reduce the

functional benefits of surgery (Escalante and Beardmore 1997).

The degree of damage to the joint and co-morbidity of other joints prior to surgery determinesthe maximal functional post-operative gain in rheumatoid arthritis. Thus, the desired level of

post-operative function should determine the timing of surgical intervention, and pre-operative function can be used as an indicator of surgical outcomes to estimate the appropriatetime for surgery (Nelissen 2003).

KEY OBJECTIVE: Promote timely joint replacement for people with rheumatoidarthritis.

Multi-disciplinary management

The care needs of people with rheumatoid arthritis vary over the course of the condition. Theinvolvement of a team of health professionals who liaise effectively with the patient, witheach other and with community resources is a model for the management of the complexneeds of people with rheumatoid arthritis (van den Hout et al 2003).

The provision of advice on the use of pharmacological and non-pharmacological treatmentsfor disease-modification and symptom management, occupational interventions, andeducation and support to assist the self-management of rheumatoid arthritis, all require input

from a range of experts. A coordinated approach to the multi-faceted care requirements ofpeople with rheumatoid arthritis appears an effective and efficient way to provide patient care,although there have been few controlled studies to date that have investigated the impact ofthis approach (Minor and Belza 2003).

5.9 Opportunities to improve the prevention and management ofrheumatoid arthritis

While a small number of risk factors and health determinants have been associated withrheumatoid arthritis, their impact on the development and progression of the disease is largelyunknown. Early treatment with disease-modifying anti-rheumatic drug therapy has thegreatest documented impact on outcome in rheumatoid arthritis (Symmons 2002).

At risk populations

The identification of people at high-risk of developing rheumatoid arthritis and those withearly features of the condition can provide a framework for improving the overall

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management of the disease (Woolf 2003). The groups at highest risk of developingrheumatoid arthritis and experiencing progression of the condition include:

People with a family history of rheumatoid arthritis; Women;

Middle to older-aged people; People who are rheumatoid factor-positive; People with inflammatory joint disease; People with radiological evidence of structural damage; People who smoke; Disadvantaged groups.

Primary prevention: whole of well population

The majority of risk factors and determinants of health associated with rheumatoid arthritisare non-modifiable. Based on current knowledge, rheumatoid arthritis does not appear to be a

preventable disease.

Opportunities for improvement

Education and behavioural modification in the following area may play a role in reducing therisk of developing rheumatoid arthritis:

Develop awareness of the risks of smoking.

KEY OBJECTIVE: Promote healthy lifestyles to optimise health outcomes.

Secondary prevention: at risk population

People at risk of developing rheumatoid arthritis and in the early stages of the condition canbenefit from secondary prevention measures to minimise progression of joint damage andsubsequent disability.


Secondary prevention of rheumatoid arthritis is targeted towards improving the speed ofdiagnosis and treatment of rheumatoid arthritis to minimise disease progression, and measuresto optimise the quality of life of people with rheumatoid arthritis:

Improve awareness of the benefits of early diagnosis and treatment among healthprofessionals and those at risk of rheumatoid arthritis;

Improve the speed of diagnosis by establishing a mechanism to ensure timely accessto specialist care;

Initiate disease-modifying drug therapy early; Provide access to educational programs with a behavioural component to help

affected individuals develop the knowledge, skills and self-confidence to managerheumatoid arthritis;

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Promote lifestyle modification and joint protection to minimise disability; Consider the need for vocational or career counselling.

KEY OBJECTIVE: Promote early and optimal management of rheumatoid arthritis to

minimise joint damage.

Tertiary prevention and disease management: population withestablished disease


Tertiary prevention and disease management involves ongoing care, support and educationstrategies to reduce symptoms and disability and improve health-related quality of life:

Provide ongoing monitoring of disease activity and response to medication; Optimise use of disease-modifying drug therapy; Optimise use of symptom-relieving measures; Provide access to joint replacement surgery to reduce pain, preserve function and

improve health-related quality of life; Provide access to interventions/aids to preserve functional independence; Manage co-morbid conditions; Use a comprehensive, multi-disciplinary approach to rheumatoid arthritis

management; Promote ongoing self-management; Provide access

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