Elsevier

The Lancet

Volume 376, Issue 9746, 25 September–1 October 2010, Pages 1094-1108
The Lancet

Seminar
Rheumatoid arthritis

https://doi.org/10.1016/S0140-6736(10)60826-4Get rights and content

Summary

Rheumatoid arthritis is characterised by persistent synovitis, systemic inflammation, and autoantibodies (particularly to rheumatoid factor and citrullinated peptide). 50% of the risk for development of rheumatoid arthritis is attributable to genetic factors. Smoking is the main environmental risk. In industrialised countries, rheumatoid arthritis affects 0·5–1·0% of adults, with 5–50 per 100 000 new cases annually. The disorder is most typical in women and elderly people. Uncontrolled active rheumatoid arthritis causes joint damage, disability, decreased quality of life, and cardiovascular and other comorbidities. Disease-modifying antirheumatic drugs (DMARDs), the key therapeutic agents, reduce synovitis and systemic inflammation and improve function. The leading DMARD is methotrexate, which can be combined with other drugs of this type. Biological agents are used when arthritis is uncontrolled or toxic effects arise with DMARDs. Tumour necrosis factor inhibitors were the first biological agents, followed by abatacept, rituximab, and tocilizumab. Infections and high costs restrict prescription of biological agents. Long-term remission induced by intensive, short-term treatment selected by biomarker profiles is the ultimate goal.

Introduction

Rheumatoid arthritis has 19th century roots and a 20th century pedigree. Although its name was introduced in the 1850s,1 classification criteria were only developed 50 years ago.2, 3 Observational studies in which these criteria are used portray treated rheumatoid arthritis as a serious long-term disease with dominant extra-articular features, limited treatment options, and poor outcomes.4, 5

Tumour necrosis factor (TNF) inhibitors and other biological agents have heralded a so-called therapeutic revolution, transforming the outlook for patients with rheumatoid arthritis. However, improved disease outcomes preceded biological agents, reflecting early use of conventional drugs, ambitious treatment goals, and better management of comorbidities. An historic parallel is the 1950s revolution in tuberculosis care, when improved conventional management followed by effective chemotherapy made tuberculosis curable.6

Section snippets

Pathophysiology

Rheumatoid arthritis is best considered a clinical syndrome spanning several disease subsets.7 These different subsets entail several inflammatory cascades,8 which all lead towards a final common pathway in which persistent synovial inflammation and associated damage to articular cartilage and underlying bone are present.

Classification and diagnosis

Early classification criteria2, 3 were designed to distinguish established rheumatoid arthritis from other types of established joint diseases (figure 2). They ensured researchers studied homogeneous patients' groups, particularly in clinical trials.

Frequency

Findings of population-based studies show rheumatoid arthritis affects 0·5–1·0% of adults in developed countries. The disease is three times more frequent in women than men. Prevalence rises with age and is highest in women older than 65 years, suggesting hormonal factors could have a pathogenic role.40 Estimates of the frequency of rheumatoid arthritis vary depending on the methods used to ascertain its presence.41, 42 Incidence ranges from 5 to 50 per 100 000 adults in developed countries and

Core measures

Assessments in rheumatoid arthritis mainly look at joint inflammation (panel).53 Doctor-based reviews include swollen and tender joint counts and global assessment (ie, overall estimates of disease activity and health status). Standard joint counts focus on 28 joints in the hands, upper limbs, and knees; joints in the feet, although important, are omitted. Some experts prefer extended 66 and 68 joint counts, which include the feet. Laboratory measures encompass erythrocyte sedimentation rate,

Assessments

Key outcomes in rheumatoid arthritis are persistent joint inflammation, progressive joint damage, and continuing functional decline.64 Other important outcomes include extra-articular features (eg, vasculitis), comorbidities (eg, cardiac disease and infections),65 and patient-related factors (eg, fatigue).66 The key treatment goal in rheumatoid arthritis is remission with no active joint inflammation and no erosive or functional deterioration. 10–50% of patients with early rheumatoid arthritis

Management

Several national and regional guidelines for management of rheumatoid arthritis exist, including recommendations from ACR, EULAR, and the UK's National Institute for Health and Clinical Excellence.77, 78, 79 Caution is needed in patients of childbearing age because many treatments have negative effects on conception and pregnancy.80

Effectiveness and cost-effectiveness

Management of rheumatoid arthritis must be effective and affordable; patients value effectiveness most whereas society emphasises affordability. Treatment costs are the first part of the economic equation. DMARDs are inexpensive whereas biological agents are costly, although technological advances could reduce future expenditure. A second component of the equation is medical costs, which are modest in the short-term but rise substantially when supportive long-term care is needed for disabling

Death and comorbidities

Patients with rheumatoid arthritis continue to have increased risks of mortality, mostly from cardiovascular disease and infection. The major causes of mortality mirror rises in specific comorbid disorders. Risks of both myocardial infarctions and strokes are amplified in individuals with rheumatoid arthritis (panel).133 Although this increase could indicate inflammation-associated vascular damage, identification and treatment of cardiovascular risk factors is important; some evidence shows

Prevention

With respect to primary prevention, decreasing the number of people who smoke within the population should reduce risk of rheumatoid arthritis developing,138 and this initiative is a realistic preventive strategy with wide health benefits. Modification of diet to prevent rheumatoid arthritis is an area of speculation; however, at present, insufficient evidence exists to support this idea.139

Looking at secondary prevention of disease, 5–15% of patients with rheumatoid arthritis from historical

Future perspectives

Although many unresolved difficulties exist for people with rheumatoid arthritis, continuing introduction of innovative treatments can overcome many of them. One key need is definition of disease subsets in individuals with early arthritis so that intensive treatment regimens can be targeted at patients who most need them and are likely to respond. We also need to move beyond long-term suppressive treatment towards short intensive therapeutic courses that result in remission. This progression

Search strategy and selection criteria

We searched the Cochrane Library (2000–09), Medline (2000–09), and Embase (2000–09). We used the search term “rheumatoid arthritis” in combination with terms relevant for every section of the article, including: “cytokines”, auto-antibodies”, genetic risk factors”, “prevalence”, “incidence”, “assessments”, “outcome measures”, “co-morbidities”, and every specific treatment approach. We mainly selected publications from the past 5 years, although we did not exclude commonly referenced and

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