Article
Rheumatoid arthritis (RA) is a progressive immune-mediated disease involving the synovium that can culminate in joint destruction, significant functional impairment, and early mortality.
ABSTRACT: An improved understanding of the pathogenesis of rheumatoid arthritis (RA) has resulted in effective new therapeutic options and a paradigm shift in the approach to treatment. The emphasis now is on early initiation of effective disease-modifying therapy to prevent joint damage and achieve disease remission. Because the 1987 American College of Rheumatology (ACR) classification criteria for RA lacked sensitivity for recognizing the earlier stages of disease, the ACR and the European League Against Rheumatism recently collaborated in an initiative to revise them. The new criteria are not a diagnostic tool but instead are intended to differentiate among patients who are at high or low risk for persistent or erosive disease or both. (J Musculoskel Med. 2011;28:422-424)
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Rheumatoid arthritis (RA) is a progressive immune-mediated disease involving the synovium that can culminate in joint destruction, significant functional impairment, and early mortality.1 An improved understanding of the pathogenesis over the past 2 decades has resulted in an explosion of effective therapeutic options. Consequently, there has been a paradigm shift in the approach to the treatment of patients who have RA-the emphasis now is on early initiation of effective disease-modifying antirheumatic drug (DMARD) therapy to prevent joint damage and achieve disease remission.1,2
TABLE
The ACR/EULAR 2010 classification criteria for RA
Years ago, it became apparent that the 1987 American College of Rheumatology (ACR) classification criteria for RA lacked sensitivity for recognizing the earlier stages of disease. With this in mind, the ACR and the European League Against Rheumatism (EULAR) recently collaborated in an initiative to revise the 1987 classification criteria (Table). The 2010 revision focuses on features found at the earlier stages of disease before the late features identified by the previous criteria develop. Note that the new criteria are not a diagnostic tool but instead are intended to differentiate among patients who are at high or low risk for persistent or erosive disease or both.3
This is the first in a series of articles that describe new or modified classification and diagnostic criteria for various rheumatologic conditions. In this article, we discuss the need for and advantages of the recently revised classification criteria for RA.
The process of developing new criteria
The ACR/EULAR joint committee included more than 35 contributors. Their aim was "to develop a set of rules to be applied to newly presenting patients with undifferentiated synovitis that would (1) identify the subset at high risk of chronicity and erosive damage; (2) be used as a basis for initiating disease-modifying therapy; and (3) not exclude the capture of patients later in the disease course."3
The new criteria were developed in 3 phases. The first phase was a data-driven approach to identify factors and their relative weights of importance that were most predictive of the decision to start methotrexate (MTX) therapy in more than 3000 patients from 9 early arthritis patient cohorts. The initiation of DMARD therapy was considered to be an indication that the patient would be at risk for persistent or erosive disease or both.
The second phase consisted of assembling an expert panel of 24 rheumatologists who refined these factors and their weights by using real-life case scenarios. They employed a consensus-based, decision science–informed approach to calculate the likelihood score of RA developing in a person; a higher score indicated a greater likelihood.
The final phase combined the findings from the first 2 phases, further refining the scoring system and determining the ideal cut point to define "definite RA." That cut point was verified by applying the new scoring system to 3 cohorts that had been included in phase 1 and to 3 cohorts that were not.3
Before the new classification criteria are applied to patients presenting with inflammatory arthritis, 2 requirements must be met: (1) there must be at least 1 joint with definite synovitis, excluding the distal interphalangeal joints, first metatarsophalangeal joints, and first carpometacarpal joints because these joints typically are affected by osteoarthritis, and (2) the synovitis cannot be explained by another disease. Four criteria are then applied, resulting in a score of 0 to 10, with 6 or higher required for the classification of definite RA.
A score lower than 6 does not classify a patient as having definite RA, but patients may meet criteria as their disease evolves over time; subsequently, they may be classified as having definite RA. In addition, patients may present at a later stage of the disease with typical RA erosions. As a result, those with long-standing disease that retrospectively would have fulfilled the 2010 criteria also should be classified as having definite RA.
How the new criteria differ from the old
The new criteria notably do not take into account such features as morning stiffness and symmetry of joint involvement as the previous criteria did. These factors were determined to be not significant. In addition, radiographic changes were excluded because they are considered late features and are not expected to be found in patients with early inflammatory arthritis.3-5
Instead, significant weight is placed on serology, with the inclusion of anti–cyclic citrullinated protein antibodies, as well as rheumatoid factor, which could account for 3 of the 6 points needed for definite RA. Ultimately, however, the diagnosis of RA remains a clinician-based decision and the new criteria are not expected to be used as a diagnostic tool.
Advantages and potential uses of the new criteria
Until now, the lack of validated and uniformly accepted criteria to classify early disease has prevented investigation of the effectiveness of earlier treatment for patients with RA. In a study conducted by van der Linden and associates,6 the 2010 criteria were found to have a sensitivity of 0.84 compared with 0.61 for the 1987 criteria when the start of MTX therapy was the outcome. The specificity was lower in the 2010 criteria but, at 0.60, was still considered acceptable.
This increased sensitivity of the new criteria for early disease associated with a poor prognosis allows for identification of patients who may benefit from early therapeutic intervention or entry into clinical trials. Consequently, the new criteria will increase the diversity of a typical RA study population, and patients at an earlier stage of the disease could be compared with those who have long-term disease. In the future, the discovery of new biomarkers is expected to lead to further revisions of the classification criteria as well as to identify additional subsets of patients to enhance personalized medicine.
Next in this series
"Axial spondyloarthritis" is a new name that encompasses ankylosing spondylitis (AS) and patients who have most features of AS but lack the typical radiographic changes of sacroiliitis. In the next article in this series, we will discuss the new Assessment of SpondyloArthritis International Society/European League Against Rheumatism Classification Criteria for Axial Spondyloarthritis.
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References
1. Breedveld FC, Combe B. Understanding emerging treatment paradigms in rheumatoid arthritis. Arthritis Res Ther. 2011;13(suppl 1):S3.
2. Wolfe F. The natural history of rheumatoid arthritis. J Rheumatol Suppl. 1996;44:13-22.
3. Aletaha D, Neogi T, Silman AJ, et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62:2569-2581.
4. Arnett FC, Edworthy SM, Bloch DA, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988;31:315-324.
5. MacGregor AJ. Classification criteria for rheumatoid arthritis. Baillieres Clin Rheumatol. 1995;9:287-304.
6. van der Linden MP, Knevel R, Huizinga TW, van der Helm-van Mil AH. Classification of rheumatoid arthritis: comparison of the 1987 American College of Rheumatology criteria and the 2010 American College of Rheumatology/European League Against Rheumatism criteria. Arthritis Rheum. 2011;63:37-42.