Evolution of treatment for rheumatoid arthritis.

Treatment for RA has changed profoundly over the past 25 years, evolving from a strategy of providing symptomatic relief, to implementation of therapeutic regimens that impact disease activity and ultimately have been shown to slow or arrest structural joint damage. Drug therapy for RA has evolved from salicylates, to NSAIDs, CSs, DMARDs, MTX, and finally to biologic response modifiers. MTX has become the initial drug of choice in most patients with RA, and some do well on MTX monotherapy without the addition of other agents. Combination regimens including MTX and other conventional DMARDs may be an effective early approach to treatment of RA. The biologic response modifiers (biologics) became available in the late 1990s, based on our understanding of the molecular mediators of synovial inflammation in RA. The first biologics inhibited TNF-α, a cytokine active in host defences against some infections and malignancies, but which also promotes inflammation and bone erosion. Inhibitors of TNF-α are mostly given with MTX, although some can be given as monotherapy. Studies consistently show that combination MTX + TNF-α inhibitor therapy leads to better outcomes than with either agent alone. Tight control strategies, employing objective measures, also lead to improved outcomes. When patients fail treatment with one or more TNF-α inhibitor + MTX, a number of other possible alternatives may be tried, including treatment with biologics having other mechanisms, such as antibodies to certain ILs, other cytokines and inflammatory mediators. Current therapy for RA is such that progression from symptom onset to significant disability is now no longer inevitable, and RA patients can anticipate comfortable and productive lives on medical therapy.

ACR/EULAR 2010 rheumatoid arthritis classification criteria.

Advances in our understanding of the pathogenesis of RA over the past two decades, particularly the identification of cytokines that promote synovial inflammation (e.g. TNF-α, IL-1 and IL-6), have led to treatment courses that affect the disease process itself, beyond alleviation of symptoms. In turn, emphasis has shifted to intervention early enough in the disease course to prevent the joint destruction that follows inflammation. Accordingly, in 2010 the ACR and the European League Against Rheumatism (EULAR) put forward revised classification criteria emphasizing RA characteristics that emerge early in the disease course, including ACPAs, a biomarker that predicts aggressive disease. These were in contrast with the 1987 ARA criteria, which distinguished established RA patients from those with other forms of arthritis, and identified patients with later disease. The categories of the 2010 ACR/EULAR criteria are grouped into four classifications, with point scores for each: joint symptoms; serology (including RF and/or ACPA); symptom duration, whether <6 weeks or >6 weeks; and acute-phase reactants (CRP and/or ESR). The criteria were developed in a three-phase process, beginning with an analysis of patient cohorts to determine what disease characteristics had persuaded clinicians to initiate MTX therapy, followed by consensus-based decisions and the creation of a scoring system that would predict which patients would go on to develop persistent and/or erosive disease.

2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative.

OBJECTIVE: The 1987 American College of Rheumatology (ACR; formerly, the American Rheumatism Association) classification criteria for rheumatoid arthritis (RA) have been criticized for their lack of sensitivity in early disease. This work was undertaken to develop new classification criteria for RA. METHODS: A joint working group from the ACR and the European League Against Rheumatism developed, in 3 phases, a new approach to classifying RA. The work focused on identifying, among patients newly presenting with undifferentiated inflammatory synovitis, factors that best discriminated between those who were and those who were not at high risk for persistent and/or erosive disease--this being the appropriate current paradigm underlying the disease construct "rheumatoid arthritis." RESULTS: In the new criteria set, classification as "definite RA" is based on the confirmed presence of synovitis in at least 1 joint, absence of an alternative diagnosis that better explains the synovitis, and achievement of a total score of 6 or greater (of a possible 10) from the individual scores in 4 domains: number and site of involved joints (score range 0-5), serologic abnormality (score range 0-3), elevated acute-phase response (score range 0-1), and symptom duration (2 levels; range 0-1). CONCLUSION: This new classification system redefines the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather than defining the disease by its late-stage features. This will refocus attention on the important need for earlier diagnosis and institution of effective disease-suppressing therapy to prevent or minimize the occurrence of the undesirable sequelae that currently comprise the paradigm underlying the disease construct "rheumatoid arthritis."

The 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for rheumatoid arthritis: Phase 2 methodological report.

OBJECTIVE: The American College of Rheumatology and the European League Against Rheumatism have developed new classification criteria for rheumatoid arthritis (RA). The aim of Phase 2 of the development process was to achieve expert consensus on the clinical and laboratory variables that should contribute to the final criteria set. METHODS: Twenty-four expert RA clinicians (12 from Europe and 12 from North America) participated in Phase 2. A consensus-based decision analysis approach was used to identify factors (and their relative weights) that influence the probability of "developing RA," complemented by data from the Phase 1 study. Patient case scenarios were used to identify and reach consensus on factors important in determining the probability of RA development. Decision analytic software was used to derive the relative weights for each of the factors and their categories, using choice-based conjoint analysis. RESULTS: The expert panel agreed that the new classification criteria should be applied to individuals with undifferentiated inflammatory arthritis in whom at least 1 joint is deemed by an expert assessor to be swollen, indicating definite synovitis. In this clinical setting, they identified 4 additional criteria as being important: number of joints involved and site of involvement, serologic abnormality, acute-phase response, and duration of symptoms in the involved joints. These criteria were consistent with those identified in the Phase 1 data-driven approach. CONCLUSION: The consensus-based, decision analysis approach used in Phase 2 complemented the Phase 1 efforts. The 4 criteria and their relative weights form the basis of the final criteria set.

2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative.

OBJECTIVE: The 1987 American College of Rheumatology (ACR; formerly the American Rheumatism Association) classification criteria for rheumatoid arthritis (RA) have been criticised for their lack of sensitivity in early disease. This work was undertaken to develop new classification criteria for RA. METHODS: A joint working group from the ACR and the European League Against Rheumatism developed, in three phases, a new approach to classifying RA. The work focused on identifying, among patients newly presenting with undifferentiated inflammatory synovitis, factors that best discriminated between those who were and those who were not at high risk for persistent and/or erosive disease--this being the appropriate current paradigm underlying the disease construct 'RA'. RESULTS: In the new criteria set, classification as 'definite RA' is based on the confirmed presence of synovitis in at least one joint, absence of an alternative diagnosis better explaining the synovitis, and achievement of a total score of 6 or greater (of a possible 10) from the individual scores in four domains: number and site of involved joints (range 0-5), serological abnormality (range 0-3), elevated acute-phase response (range 0-1) and symptom duration (two levels; range 0-1). CONCLUSION: This new classification system redefines the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather than defining the disease by its late-stage features. This will refocus attention on the important need for earlier diagnosis and institution of effective disease-suppressing therapy to prevent or minimise the occurrence of the undesirable sequelae that currently comprise the paradigm underlying the disease construct 'RA'.

Mesenteric involvement in giant cell arteritis. An underrecognized complication? Analysis of a case series with clinicoanatomic correlation.

We reviewed the clinical manifestations of mesenteric vasculitis due to giant cell arteritis (GCA) and considered features of the mesenteric anatomy in relationship to disease expression. We compiled and reviewed a case series by systematic identification of patients previously reported in the English-language literature to have mesenteric involvement from known GCA. Included in the analysis was a detailed case review of a patient with GCA and small bowel infarction seen at our institution. Twelve patients were identified with mesenteric ischemia attributed to GCA. Concomitant cranial and abdominal symptoms were present in 7 of the 12 patients, and cranial symptoms were absent in 5 patients who presented with abdominal complaints. The abdominal symptoms fell within a spectrum ranging from chronic postprandial symptoms to acute abdominal pain. Survival was observed in only 6 of the 12 cases, 3 of whom required bowel resection and were treated with high-dose corticosteroids. Review of the anatomic features of the specialized splanchnic circulation reveals an extensive collateral network that may protect against early disease expression from ischemia, despite mesenteric arteritic involvement. Mesenteric vasculitis resulting in small bowel infarction has only rarely been described in GCA but represents a serious and potentially treatable complication. We propose an explanation, based on mesenteric vascular anatomy, for the infrequency of symptomatic expression of this entity and suggest that occult mesenteric GCA may be present far more often than recognized.