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
SeminarRheumatoid arthritis
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
References (139)
- et al.
Long-term outcome of treating rheumatoid arthritis: results after 20 years
Lancet
(1987) - et al.
Rheumatoid arthritis
Cell
(1996) - et al.
Adoptive transfer of IL-10-secreting CD4(+)CD49b(+) regulatory T cells suppresses ongoing arthritis
J Autoimmun
(2010) - et al.
Gene-gene and gene-environment interactions involving HLA-DRB1, PTPN22, and smoking in two subsets of rheumatoid arthritis
Am J Hum Genet
(2007) - et al.
Low and stable prevalence of rheumatoid arthritis in northern France
Joint Bone Spine
(2009) - et al.
Rheumatoid arthritis in the developing world
Best Pract Res Clin Rheumatol
(2003) - et al.
The Simplified Disease Activity Index and Clinical Disease Activity Index to monitor patients in standard clinical care
Rheum Dis Clin North Am
(2009) - et al.
Radiographic measures to assess patients with rheumatoid arthritis: advantages and limitations
Rheum Dis Clin North Am
(2009) - et al.
The course of established rheumatoid arthritis
Best Pract Res Clin Rheumatol
(2007) - et al.
Extra-articular manifestations and complications of rheumatoid arthritis
Best Pract Res Clin Rheumatol
(2007)
Chronic arthritis before 1876: early British cases suggesting rheumatoid arthritis
Ann Rheum Dis
1958 revision of diagnostic criteria for rheumatoid arthritis
Arthritis Rheum
The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis
Arthritis Rheum
Prediction of long-term mortality in patients with rheumatoid arthritis according to simple questionnaire and joint count measures
Ann Intern Med
Commentary: medicine, population, and tuberculosis
Int J Epidemiol
Advances in the genetics of rheumatoid arthritis point to subclassification into distinct disease subsets
Arthritis Res Ther
Differences in synovial tissue infiltrates between anti-cyclic citrullinated peptide-positive rheumatoid arthritis and anti-cyclic citrullinated peptide-negative rheumatoid arthritis
Arthritis Rheum
Therapeutic benefit of blocking interleukin-6 activity with an anti-interleukin-6 receptor monoclonal antibody in rheumatoid arthritis: a randomized, double-blind, placebo-controlled, dose-escalation trial
Arthritis Rheum
Synovial fibroblasts of patients with rheumatoid arthritis attach to and invade normal human cartilage when engrafted into SCID mice
Am J Pathol
Invasiveness of fibroblast-like synoviocytes is an individual patient characteristic associated with the rate of joint destruction in patients with rheumatoid arthritis
Arthritis Rheum
Denosumab treatment effects on structural damage, bone mineral density, and bone turnover in rheumatoid arthritis: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial
Arthritis Rheum
Mr Outside and Mr Inside: classic and alternative views on the pathogenesis of rheumatoid arthritis
Ann Rheum Dis
Synovial fibroblasts spread rheumatoid arthritis to unaffected joints
Nat Med
Effective treatment of collagen-induced arthritis by adoptive transfer of CD25+ regulatory T cells
Arthritis Rheum
Value of anti-modified citrullinated vimentin and third-generation anti-cyclic citrullinated peptide compared with second-generation anti-cyclic citrullinated peptide and rheumatoid factor in predicting disease outcome in undifferentiated arthritis and rheumatoid arthritis
Arthritis Rheum
Isotype distribution of anti-cyclic citrullinated peptide antibodies in undifferentiated arthritis and rheumatoid arthritis reflects an ongoing immune response
Arthritis Rheum
Marked differences in fine specificity and isotype usage of the anti-citrullinated protein antibody in health and disease
Arthritis Rheum
Structure and pathogenicity of antibodies specific for citrullinated collagen type II in experimental arthritis
J Exp Med
Evidence for a functional role of IgE anticitrullinated protein antibodies in rheumatoid arthritis
Proc Natl Acad Sci USA
Antibodies to citrullinated proteins and differences in clinical progression of rheumatoid arthritis
Arthritis Res Ther
Quantitative heritability of anti-citrullinated protein antibody-positive and anti-citrullinated protein antibody-negative rheumatoid arthritis
Arthritis Rheum
Genetic susceptibility to rheumatoid arthritis: an emerging picture
Arthritis Rheum
Association of CD40 with rheumatoid arthritis confirmed in a large UK case-control study
Ann Rheum Dis
Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci
Nat Genet
Recent progress in rheumatoid arthritis genetics: one step towards improved patient care
Curr Opin Rheumatol
Refining the complex rheumatoid arthritis phenotype based on specificity of the HLA-DRB1 shared epitope for antibodies to citrullinated proteins
Arthritis Rheum
Cutting edge: the conversion of arginine to citrulline allows for a high-affinity peptide interaction with the rheumatoid arthritis-associated HLA-DRB1*0401 MHC class II molecule
J Immunol
Sensitivity and specificity of the American College of Rheumatology 1987 criteria for the diagnosis of rheumatoid arthritis according to disease duration: a systematic literature review and meta-analysis
Ann Rheum Dis
Changes over time in the diagnosis of rheumatoid arthritis in a 10 year cohort
J Rheumatol
Efficacy of methotrexate treatment in patients with probable rheumatoid arthritis: a double-blind, randomized, placebo-controlled trial
Arthritis Rheum
Impact of T-cell costimulation modulation in patients with undifferentiated inflammatory arthritis or very early rheumatoid arthritis: a clinical and imaging study of abatacept (the ADJUST trial)
Ann Rheum Dis
Validation of a prediction rule for disease outcome in patients with recent-onset undifferentiated arthritis: moving toward individualized treatment decision-making
Arthritis Rheum
Validation of a prediction rule for development of rheumatoid arthritis in patients with early undifferentiated arthritis
Ann Rheum Dis
A prediction rule for disease outcome in patients with undifferentiated arthritis using magnetic resonance imaging of the wrists and finger joints and serologic autoantibodies
Arthritis Rheum
The prevalence of rheumatoid arthritis in the United Kingdom: new estimates for a new century
Rheumatology (Oxford)
Measuring disease prevalence: a comparison of musculoskeletal disease using four general practice consultation databases
Br J Gen Pract
Rheumatoid arthritis in UK primary care: incidence and prior morbidity
Scand J Rheumatol
The incidence of rheumatoid arthritis in Spain: results from a nationwide primary care registry
Rheumatology (Oxford)
Incidence of rheumatoid arthritis from 1995 to 2001: impact of ascertainment from multiple sources
Rheumatol Int
Cited by (2700)
Microstructural abnormality of white matter tracts in rheumatoid arthritis
2024, Brain ResearchSinomenine ameliorates fibroblast-like synoviocytes dysfunction by promoting phosphorylation and nuclear translocation of CRMP2
2024, Journal of EthnopharmacologyImmune cell-derived extracellular vesicles for precision therapy of inflammatory-related diseases
2024, Journal of Controlled ReleasePeptide targeting improves the delivery and therapeutic index of glucocorticoids to treat rheumatoid arthritis
2024, Journal of Controlled Release