Disease outcome and functional capacity in rheumatoid arthritis

INTRODUCTION — Rheumatoid arthritis (RA) has a variable disease course that can potentially result in physical disability, work-loss, increased risk of certain comorbid illnesses, and early death. However, effective, timely treatment is likely to modify disease activity and disease progression and can improve long-term outcomes.

Functional capacity, comorbidities, and mortality in RA are reviewed here. Specific instruments for assessment of disease activity and function, clinical manifestations of RA, and strategies for effective disease management are described separately. (See "Assessment of rheumatoid arthritis disease activity and physical function" and "Clinical manifestations of rheumatoid arthritis" and "Overview of the systemic and nonarticular manifestations of rheumatoid arthritis" and "General principles and overview of management of rheumatoid arthritis in adults".)

DISEASE COURSE AND OUTCOME — The course of rheumatoid arthritis (RA) is variable [1]; both short- and long-term disease outcomes, which can benefit from early and aggressive treatment, depend upon multiple factors [2]. Most patients have progressive disease, which can take either a slow or a rapid course, and approximately 15 to 20 percent of patients have intermittent disease with periods of exacerbation and a relatively good prognosis. (See "Clinical manifestations of rheumatoid arthritis".)

The outcome of RA depends upon several factors, including the degree of joint damage, the physical functional status of the patient, psychological health, and the presence of comorbid illnesses (see 'Functional outcomes' below). These comorbidities include cardiovascular, pulmonary and infectious disease; certain cancers; and other disorders. A reduced life expectancy can be seen in some patients with severe RA, due to illnesses that may be the result of RA itself or the drugs used in its treatment (table 1). (See 'Impact of comorbidities' below and 'Mortality' below.)

A treatment approach that focuses on aggressive management early in the disease course, with an emphasis on attaining and maintaining low articular disease activity or remission, is associated with improved life expectancy for people with RA and a reduction in the prevalence of some RA-associated comorbidities. (See "General principles and overview of management of rheumatoid arthritis in adults", section on 'Management strategies' and 'Impact of comorbidities' below and 'Impact of therapy' below.)

FUNCTIONAL CAPACITY

Factors affecting physical function and disability — Loss of functional capacity in rheumatoid arthritis (RA) is a result of the summation of loss of function in individual joints, but is also affected by muscle function and metabolic factors:

●Joint function – Individual joint function depends upon numerous factors:

•Severity of disease activity (ie, burden of synovitis)

•Structural integrity of a joint

•Muscle strength and tone

•General fitness of the patient

•Psychosocial factors

The articular component of functional disability is predominantly due to inflammatory synovitis during the early stage of the disease, loss of structural integrity of joints at a late stage, and, depending upon the level of disease activity, a combination of both for the rest of the course of disease [3].

While recognizing the limitations of self-reports of physical function, there is evidence that the common-sense notion that the combination of inflammation and joint damage leads to functional limitation is correct. This was illustrated by the results of a Finnish population-based survey of 1095 patients with an established diagnosis of RA and 1530 age- and sex-matched controls [4]. A score on the Health Assessment Questionnaire (HAQ) of more than 1 suggests that a person is having difficulty with most activities of daily living. Patients were nearly eight times more likely to report moderate disability (HAQ score ≥1) than controls.

●Body composition – The effect of RA inflammation and joint damage on physical function appears to extend beyond the direct effects of synovitis and erosive joint damage; RA patients tend to have lower muscle mass, lower muscle density, and more body fat compared with otherwise similar individuals without RA [5-7].

Individuals with RA who had lower muscle mass, particularly lower density muscle, and higher fat mass reported worse physical function and demonstrated lower scores on physical performance testing compared with those with better muscle and fat composition [7,8]. Patients with RA who were obese also had worse disease and a poorer response to anti-tumor necrosis factor (TNF) therapy [9]. The effects of body composition on performance were as great as or greater than the contributions from synovitis, joint deformity, and psychosocial factors. Notably, physical function among those with higher levels of joint swelling and/or deformity was better for those with more optimal body composition compared with those with similar levels of articular disease activity and damage but with suboptimal fat and muscle composition [10].

●Psychosocial factors – Psychosocial factors are an important component of the non-articular issues that may adversely affect functional status. These factors that affect psychosocial health and function, including learned helplessness, reduced sense of self-efficacy, and depression, may account for an estimated 10 to 20 percent of disability measured by both questionnaire-based instruments and by tests of walking speed [10-12].

Assessment of functional status — A number of instruments (eg, the Stanford HAQ and its modifications) have been developed for quantitative structured assessment of patients' functional status, an outcome of direct importance to patients with RA. These measures are useful for the assessment of patient outcomes in clinical practice, in response to specific therapies in clinical trials, and for the study of the natural history and course of disease over time. (See "Assessment of rheumatoid arthritis disease activity and physical function", section on 'Assessment of physical function'.)

●Instruments for routine clinical use – Three patient-reported functional status assessment measures for RA have been endorsed for clinical use by the American College of Rheumatology based upon consideration of both psychometric/clinimetric properties and ease of use in the clinical setting [13]:

•The HAQ-II and the Multidimensional HAQ (MD-HAQ), which are both modifications of the more detailed original HAQ [14-20]. The MD-HAQ is used as a component of the Routine Assessment of Patient Index Data 3 (RAPID3) disease activity assessment instrument that is increasingly utilized in routine clinical practice [21]. The forms for the HAQ, the HAQ-II, and the MD-HAQ can be obtained from online sources (eg, rheuminfo.com/physician-tools/health-assessment-questionnaires-haq-haq-ii-mdhaq/). (See "Assessment of rheumatoid arthritis disease activity and physical function", section on 'Health Assessment Questionnaire (HAQ)' and "Assessment of rheumatoid arthritis disease activity and physical function", section on 'Routine Assessment of Patient Index Data 3 (RAPID3)'.)

•The 10-item Patient-Reported Outcomes Measurement Information System (PROMIS) physical function questionnaire, which was not developed based on the legacy HAQ instrument. It can be obtained from the National Institutes of Health (NIH) website (https://www.healthmeasures.net/explore-measurement-systems/promis). (See "Assessment of rheumatoid arthritis disease activity and physical function", section on 'Physical Function 10-item Short Form (PROMIS PF10a)'.)

Patient-reported functional disability measures were developed as a result of a series of efforts to classify and grade functional capacity based upon the patient's ability to undertake daily activities in the home, at work, or during leisure time. The functional status questionnaires are limited, however, by their emphasis on the physical impact of RA, rather than the psychological health of the patient or the familial, social, and financial consequences of the disease. Indeed, further studies have suggested that psychosocial factors may contribute between 10 to 20 percent towards disability (see 'Factors affecting physical function and disability' above). All of these important issues contribute to the patient's quality of life [22]. Thus, a holistic approach to managing patients with RA requires careful attention to many potential consequences of this chronic disease.

●Other measures – Another of the initial well-studied and validated functional disability indices based on self-report questionnaires and which was used for this purpose included the Arthritis Impact Measurement Scale Health Status Questionnaire (AIMS) [23]. However, the complexity of this questionnaire, like the HAQ, and the time required for completion led to its modification and simplification for use in routine management.

FUNCTIONAL OUTCOMES

Long-term outcomes — Long-term functional outcomes for patients with rheumatoid arthritis (RA) vary widely, but most studies have shown improved outcomes with early effective intervention with disease-modifying antirheumatic drugs (DMARDs) and use of approaches favoring tight control of disease activity.

●Range of long-term outcomes – The long-term functional outlook is variable for patients who present early in the course of their illness and are treated. As an example, in a 2002 report of a study that prospectively followed 168 Swedish patients for 10 years or more, 94 percent continued to be independent in their daily activities [24]. The proportions of those with "almost no disability," mild, moderate, and serious disability based on the HAQ were 20, 28, 48, and 10 percent, respectively, at the end of observation. Almost 20 percent of patients had quiescent disease when last examined.

●Impact of therapeutic advances – Use of effective DMARDs and DMARD treatment strategies has been increasing, and this may be having a favorable effect on the severity of disability of patients with RA, in particular, the more widespread adoption of the treat-to-target approach with low disease activity or remission as the target. Among 472 Dutch RA patients enrolled in an observational cohort using a treat-to-target protocol aimed at remission induction, those who achieved remission within the first six months of disease had Health Assessment Questionnaire (HAQ) scores at one year that were approximately half of those who did not achieve early remission [25]. Differences were maintained at three years but narrowed slightly by five years of follow-up. This narrowing in the difference in HAQ was due to increases in HAQ in the early-remission group between three and five years of follow-up, although it should be noted that the increases, on average, were less than the established minimal clinically important change in HAQ of 0.22 to 0.25 units.

Some studies indicate that the trend towards more aggressive and early RA treatment in the early 21^st century may not have reduced the risk of long-term disability as expected. A study of 8678 patients from the Swiss national RA cohort found that disability scores (measured by the HAQ) worsened by 1.8 percent per year [26]. A second study of 2500 patients from 3 prospective cohorts found that patients with equivalent levels of inflammation may still have different long-term outcomes (measured by the HAQ) [27]. In this study, higher levels of fatigue, depression, and pain were all associated with higher levels of long-term disability.

Those with autoantibody-positive RA exhibit the largest temporal improvement in HAQ for the most recent treatment era compared with past eras [28]. Autoantibody-negative RA patients showed little temporal change in how their HAQ responded to treatment across eras.

●Long-term benefits of early intervention – The beneficial effects of antirheumatic drug treatment on function may be determined, at least in part, by the amount of joint damage that is present at the time such therapy is initiated. This was illustrated in retrospective study data from two trials that had randomly assigned patients with moderate to severe RA, who had not responded fully to methotrexate (MTX), to receive either infliximab or placebo [29,30]; improvement in function as measured by HAQ was inversely correlated with the amount of baseline radiographic damage [31]. These findings suggest that interventions that are effective in preventing joint damage may be most effective in improving function when introduced as early as possible. (See "General principles and overview of management of rheumatoid arthritis in adults", section on 'Management strategies'.)

Impact on employment — RA may impact the ability to earn a living, but the degree of this impact is uncertain; the ability to work among patients with RA has improved over the last three decades, and has been shown to vary depending upon a number of factors, including disease activity and physical function, work-environment, educational level, and potential for adapting work to limitations posed by the disease [32-38]. Work productivity may be adversely affected even when employment is maintained.

Early studies suggested that employment of patients with RA was approximately one-half that of unaffected individuals [37,38]. However, subsequent surveys report similar employment rates among patients with or without RA. As an example, after adjustment for level of education, sex, and age among individuals in the Netherlands, the rates of employment for patients with RA compared with that of the general population were not significantly different (61 versus 65 percent, respectively) [32]. A subsequent study from Sweden suggested that treatment with tumor necrosis factor (TNF) inhibitors was associated with a 35 percent increase in employment rate, suggesting that biologic therapy may have had additional benefit [33].

Important factors that influence capacity to maintain employment include:

●Increased risk of work disability – The following features related to RA have been noted to increase the likelihood of being unable to work [34-36]:

•Pain

•Impaired physical function

•Difficulty commuting to work

•Failure of antirheumatic drug therapy to produce significant improvement in disease activity, using measurements such as the ACR 20 percent response (ACR20) and Disease Activity Scores (eg, DAS28)

●Decreased risk of work disability – The presence of other factors is significantly associated with a decreased risk of being disabled, including [34,36]:

•Being self-employed

•Having ergonomic improvements made at the work site

•Reporting a positive attitude about the importance of work

•Having at least an ACR20 response to antirheumatic therapy

Employment status (ie, whether a patient is working or not) does not fully capture the economic impact of the disease as it relates to the workplace. The productivity of patients who continue to work may be adversely affected by disease-related absences and work restrictions [39].

A number of instruments assessing work-productivity, several of which are RA specific, have been evaluated in the context of arthritis [40]. While typically used in the research setting, the RA-specific instruments (the Rheumatoid Arthritis Specific Work Productivity Survey [WPS-RA] and the Work Instability Scale for Rheumatoid Arthritis [RA-WIS]) have the potential to be used in clinical practice. The WPS-RA has 9 questions and is easy to administer and score. Permission is required for its use. The RA-WIS has 23 questions and takes more time than the WPS-RA to administer and score. It is copyrighted and also requires permission to use.

IMPACT OF COMORBIDITIES

Range of disorders and causes — People with rheumatoid arthritis (RA) tend to have an increased prevalence of other serious comorbidities; the most common include infection, renal impairment, lymphoma, depression, gastroduodenal ulcer disease, asthma, chronic obstructive pulmonary disease (COPD), solid malignancies, and ischemic cardiovascular disease [41,42].

The bases for the prevalence of these comorbidities in RA include the following:

●The specific comorbidity and RA share risk factors (eg, smoking is a risk factor for both RA and asthma/COPD).

●RA causes the comorbidity (eg, chronically elevated inflammatory cytokines accelerate atherogenesis).

●The pain and debility of RA contribute to the comorbidity (eg, depression).

●RA pharmacotherapies are risk factors for the comorbidity (eg, nonsteroidal antiinflammatory drugs [NSAIDs] are risk factors for gastric ulcers and cardiovascular disease, and glucocorticoids are risk factors for infection).

RA patients often have multiple concomitant comorbidities. In a study of over 100,000 patients with RA, the odds of having two or three comorbid diseases were greater than two-fold higher for people with RA compared with non-RA controls [43], and RA patients accumulated more additional comorbidities over time than the non-RA group. Individuals' comorbidities and, particularly, multimorbidity contribute to physical dysfunction and the reduced quality of life associated with RA [44] and can even be fatal.

The impact of comorbidities on disease management is described separately. (See "General principles and overview of management of rheumatoid arthritis in adults", section on 'Comorbidities and disease management'.)

Infection — Infections, particularly pulmonary, skin, and joint infections, occur with increased frequency in RA [45]. The reason is incompletely understood, but the following factors may contribute [46]:

●Immunosuppression by the disease itself or its treatment, including glucocorticoids and biologic disease-modifying antirheumatic drugs (DMARDs)

●The presence (often subclinical) of inflammatory lung disease

●An increase in cigarette smoking

●Multiple factors associated with disability and immobility

Immunosuppression from use of glucocorticoids and immunosuppressive agents is probably the most important [47]. However, the highest glucocorticoid doses are used in the patients with most active disease, which also may contribute to the infection risk. Consistent with this hypothesis is the observation in a population-based study of 609 RA patients and an equal number of controls that RA remained an independent risk factor for infection after adjustment for glucocorticoid use, leukopenia, age, cigarette smoking, and diabetes [45]. Infections that required hospitalization were more common among patients with RA, compared with controls (adjusted hazard ratio 1.83, 95% CI 1.52-2.21). (See "Major adverse effects of systemic glucocorticoids".)

In contrast with the increased risk of infection associated with the use of glucocorticoids and potent immunosuppressives, the use of nonbiologic (conventional synthetic) DMARDs (csDMARDs) does not appear to be associated with an increased risk of infection. This was illustrated in a retrospective study of 27,710 Canadian patients with RA, in which the risk of serious infection among patients not taking glucocorticoids was similar in both DMARD users and nonusers [48]. In contrast to csDMARDs, all available biologic DMARDs are associated with an increased risk of infections. In a 2019 meta-analysis , overall infection risk among over 11,000 RA patients treated with Janus kinase (JAK) inhibitors was not increased, compared with patients on conventional DMARDs [49]. One exception was a nearly threefold increase in herpes zoster infections.

Neutropenia and increased susceptibility to infection are consequences of both Felty syndrome and the large granular lymphocyte syndrome (see "Clinical manifestations and diagnosis of Felty syndrome"). Even in the absence of the full-blown syndrome, mild lymphopenia is very common in RA and may increase the susceptibility to infection. Lymphopenia commonly occurs with glucocorticoid treatment, and both csDMARDS and targeted synthetic DMARDs (tsDMARDs), but it is rarely of clinical significance.

Renal disease — Renal disease directly related to RA is rare, and chronic inflammation and drug-related renal disease are very infrequent causes of renal compromise as well. Renal diseases associated with RA are described in more detail separately. (See "Overview of the systemic and nonarticular manifestations of rheumatoid arthritis", section on 'Kidney disease'.).

Secondary (AA) amyloidosis due to chronic inflammation is possible, although trends to more aggressive RA management have made observing this outcome rare. Membranous nephropathy due to gold and penicillamine use is no longer observed, since these drugs are no longer part of the treatment regimen for RA. Although NSAID use is still frequent in RA, NSAID prevalence and dose are lower than in previous eras. Thus, NSAID nephrotoxicity is now relatively uncommon in the RA population. (See "Membranous nephropathy: Pathogenesis and etiology" and "Causes and diagnosis of AA amyloidosis and relation to rheumatic diseases" and "NSAIDs: Acute kidney injury".)

Lymphoproliferative disorders — Lymphoproliferative disorders occur with increased frequency in patients with RA; incidence and mortality rates due to leukemia or lymphoma are approximately twofold higher than expected; the lymphoma incidence increases as active RA persists and correlates with the severity of disease activity. Additionally, drugs used to treat the disease, including alkylating agents, azathioprine, methotrexate (MTX), potentially biologic DMARDs, and tsDMARDs, may contribute to the risk, although not all patients with RA who develop malignancies have been treated with any of these agents. The etiology of neoplasia in such patients may include immune dysregulation and/or chronic immune activation. The evidence supporting these observations is described separately. (See "Hematologic complications of rheumatoid arthritis", section on 'Hematologic malignancies'.)

Up to one-third of patients with the large granular lymphocyte (LGL) leukemia have RA and may fulfill the clinical criteria for Felty syndrome. LGL leukemia in RA is discussed in detail separately. (See "Large granular lymphocyte leukemia in rheumatoid arthritis".)

Cardiovascular disease — Observational studies suggest that RA is associated with an increased risk of cardiovascular disease that appears to correlate with the activity and duration of the RA. This issue is discussed in detail separately. (See "Coronary artery disease in rheumatoid arthritis: Implications for prevention and management" and "Coronary artery disease in rheumatoid arthritis: Pathogenesis, risk factors, clinical manifestations, and diagnostic implications" and "Heart failure in rheumatoid arthritis".)

MORTALITY

Increased mortality rates — Rheumatoid arthritis (RA) is a potentially fatal illness; levels of premature all-cause mortality relative to the general population appear to be decreasing, but cardiovascular risks remain elevated in most studies [50-54].

As examples, a nationwide Norwegian cohort study of 36,095 patients with RA demonstrated that RA is associated with an increase in all-cause mortality (hazard ratio 1.45, 95% CI 1.41-1.48), primarily due to cardiovascular disease, neoplasm, and respiratory illness [55]. Another study, involving 3501 patients with RA followed for up to 35 years, found that mortality was increased twofold, resulting in a decreased lifespan of 7 to 10 years (figure 1) [51]. Other studies have shown that RA patients have a 50 percent increased risk of premature mortality, with life expectancy decreased by 3 to 10 years [56]. Mortality directly due to RA itself was low (9.8 percent of the deaths), although precise causes were not reported.

A portion of the marked increase in mortality in some reports may reflect referral bias, as many of these patients were being treated in large tertiary care centers. In a community-based study of 450 adult patients with RA, for example, the increased death rate was somewhat less than that observed in large medical centers [57]. The ratio of observed to expected deaths (standardized mortality ratio [SMR]) was 1.38 overall, with women bearing the highest risk (SMR of 1.55 and 1.07 for females and males, respectively). Additional data reported in 2003 based upon analysis of this almost exclusively White North American population confirmed a modest age- and sex-adjusted increase in mortality rates (SMR 1.27, 95% CI 1.13-1.41) with no significant change in the risk of premature death during the 40-year period of observation [58].

Improvements in therapy have not yet normalized survival for all populations with RA relative to the general population, although evidence of a narrowing of the mortality gap for patients with RA comes from a 2021 report from Denmark, which found similar 10-year all-cause mortality for patients with RA and the general population, although rates of cardiovascular disease remained higher among patients with RA [59]; and some studies continue to show a gap between mortality rates in patients with RA and the improving mortality rate in the general population [56]. Meta-analyses from 2008 and 2009 have also shown a 50 to 60 percent increased risk of mortality from cardiovascular disease [60,61]; and one of these studies showed no change in SMR over a 50-year period [61]. By contrast, in another study, in which patients with RA were followed from 1980 to 1997, lower rates of death due to acute myocardial infarction, which were similar to the general population, were noted in the patients diagnosed and treated in the 1990s [62].

Risk factors for premature mortality — Independent predictors of mortality primarily include markers associated with increased clinical severity [51,56,63-65]. These include age, lower educational level, male sex (figure 1), reduced physical function, rheumatoid factor and anti-citrullinated peptide antibodies, rheumatoid nodules, elevated erythrocyte sedimentation rate and C-reactive protein, elevated Disease Activity Score in 28 joints (DAS28 score), greater joint counts, use of NSAIDs and of glucocorticoids.

Other factors associated with an increased mortality rate include a lower than ideal body weight (body mass index <20) [66], the presence of extraarticular disease, depression [67], circulating immune complexes [52], increased levels of soluble tumor necrosis factor receptors [68], and the presence of certain human leukocyte antigen (HLA) DRB1 alleles [69]. (See "HLA and other susceptibility genes in rheumatoid arthritis".)

Causes of death — The more common causes of death in patients with RA have been related to comorbid illnesses, particularly cardiovascular and cerebrovascular disease, infection, lymphomas, and gastrointestinal bleeding. Mechanisms by which premature mortality can occur in RA also include amyloidosis, transection of the cord due to cervical spine instability, and respiratory failure due to interstitial lung disease.

Patients with RA with a first cardiovascular event appear to have a higher mortality rate during the subsequent 30 days than those without RA (18 versus 11 percent) [70]. The reason for the difference in fatalities is uncertain. Possible explanations include a greater prevalence of severe epicardial coronary artery disease in patients with RA who present with new ischemic symptoms [71] and the presence of small vessel disease that is not amenable to angioplasty or bypass surgery [72].

Some studies have found a decrease or at least no increase in the expected number of deaths from cancer, probably reflecting the increase from other causes [73]. However, one large study of over 20,000 patients with RA reported an increased incidence of death resulting from lung cancer [74]. (See "Malignancy and rheumatic disorders", section on 'Rheumatoid arthritis'.)

Impact of therapy — Patients who respond to therapy, particularly a disease-modifying antirheumatic drug (DMARD), may have lower mortality, as shown in observational studies involving methotrexate (MTX) and biologic DMARDs:

●Methotrexate:

•One long-term prospective study of 271 patients begun on MTX found that the group with more than 50 percent improvement had a less elevated rate of observed to expected deaths (standardized mortality ratio [SMR]) compared with patients who had no improvement or who had discontinued treatment (SMR 1.47 versus 4.11 and 5.56, respectively) [75].

•In an observational study of a cohort of 1240 patients with RA at an outpatient arthritis center in North America with a total of 191 deaths. MTX was prescribed for 588 patients [76]. The group that received MTX had poorer prognostic indicators. After adjustment for confounding by indication and other factors the hazard ratio for all-cause mortality among MTX-treated patients compared with nonusers was 0.4 (95% CI 0.2-0.8). The mortality risk from cardiovascular disease was lower than the trend for reduced noncardiovascular mortality (0.3 versus 0.6). The patients in this study were treated beginning in the 1980s and 1990s, prior to the general availability of biologic DMARDs. Use of conventional synthetic DMARDs other than MTX did not result in any survival advantage.

●Biologic DMARDs:

•In a post-hoc analysis of pooled safety data from clinical trials of the tumor necrosis factor (TNF) inhibitor adalimumab for patients with RA, treated patients had a lower SMR compared with the general population [77], although this finding could be confounded by the general exclusion of sicker patients from clinical trials. Similar results were seen in analyses of patients in trials of adalimumab for other inflammatory disorders.

•In a study based upon data from the German RABBIT registry (comprising 8908 patients with RA), a lower risk of mortality was observed among those treated with TNF inhibitors, rituximab, and other biologic DMARDs compared with biologic-naïve patients prescribed methotrexate (adjusted hazard ratios 0.64, 95% CI 0.50-0.81; 0.57, 95% CI 0.39-0.84; and 0.64, 95% CI 0.42-0.99; respectively) [78].

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Beyond the Basics topics (see "Patient education: Rheumatoid arthritis symptoms and diagnosis (Beyond the Basics)" and "Patient education: Rheumatoid arthritis treatment (Beyond the Basics)")

SUMMARY

●The outcome of rheumatoid arthritis (RA) depends upon the degree of disease activity, joint damage, the physical functional status of the patient, psychological health, and the presence of comorbid illness. (See 'Disease course and outcome' above.)

●Loss of functional capacity in RA is a result of the summation of loss of function in individual joints, which depends upon numerous factors. Since functional capacity is an important determinant of the natural history of RA and is a useful tool for assessing the effectiveness of therapeutic interventions, many instruments for patient evaluation have been developed. (See 'Functional capacity' above and 'Assessment of functional status' above.)

●The long-term functional outlook is variable for patients who present early in the course of their illness and are treated. The combination of inflammation and joint damage leads to functional impairment. The impact of RA on the ability to earn a living is uncertain. (See 'Long-term outcomes' above and 'Impact on employment' above.)

●Patients with RA have an increased prevalence of other serious illnesses. The predominant conditions contributing to the comorbidity and mortality of RA are (table 1) (see 'Impact of comorbidities' above):

•Infections, particularly pulmonary, skin, and joint infections, which occur with increased frequency in RA (see 'Infection' above)

•Renal impairment, which is uncommon but may be due to RA itself or drug therapy (see 'Renal disease' above)

•Lymphoproliferative disorders, including lymphoma, which occur with increased frequency in patients with RA (see 'Lymphoproliferative disorders' above)

•Cardiovascular disease, which appears to correlate with the activity and duration of the RA (see 'Cardiovascular disease' above)

●RA patients have an increased risk of premature mortality, and their life expectancy is decreased, although most of the mortality is not due directly to RA itself. (See 'Mortality' above.)

ACKNOWLEDGMENTS — The UpToDate editorial staff acknowledges Ravinder N Maini, BA, MB BChir, FRCP, FMedSci, FRS and PJW Venables, MA, MB BChir, MD, FRCP, who contributed to earlier versions of this topic review.