During the last decades, the focus of the management of rheumatoid arthritis (RA) has shifted to the early phase of the disease. This change was fueled by studies showing that early achievement of a low disease activity state is beneficial for the further course of RA. These studies raised awareness regarding the importance of early treatment and pointed to the relevance of early recognition of RA. From this perspective, the 1987 American College of Rheumatology (ACR) criteria for RA (1) have been criticized, because they are not equipped to diagnose early RA. This is not surprising, because the 1987 criteria were developed in order to define homogeneous patient groups for research purposes and therefore were based on patients in whom the average disease duration was 7 years.
In order to be able to identify patients with early RA for clinical trials and other studies, new classification criteria for RA were derived by a task force of experts from both the European League Against Rheumatism (EULAR) and the ACR (2). The main purpose of these 2010 criteria is to achieve increased sensitivity and specificity for identifying RA in an early phase.
At present, the diagnostic and discriminative abilities of these new criteria are not known. In addition, it is unclear how the 2010 ACR/EULAR criteria perform in relation to the 1987 ACR criteria. This is especially relevant, because the working group that developed the 2010 criteria stressed in their discussion that patients fulfilling the 2010 criteria are probably less homogeneous and, therefore, that in clinical trials, researchers should “document the proportions of study subjects who fulfill the previous (1987) criteria and the new RA classification criteria, to enable comparisons.” Moreover, the working group warned that the 2010 criteria may increase heterogeneity by including different phenotypes, thereby making basic science studies more difficult.
Therefore, the present study evaluated the following questions: What proportion of patients with early arthritis who do not fulfill the 1987 criteria can, according to the 2010 criteria, be classified as having RA? Do all patients with early arthritis who fulfill the 1987 criteria fulfill the 2010 criteria as well? Do patients with RA indeed fulfill the 2010 criteria at an earlier point in time than they would have using the 1987 criteria? In addition, the sensitivity and specificity of the 2010 criteria for RA were assessed. For this analysis, 3 outcome measures were studied: initiation of methotrexate (MTX), initiation of any disease-modifying antirheumatic drug (DMARD), and having persistent arthritis over a 5-year followup period.
- Top of page
- PATIENTS AND METHODS
- AUTHOR CONTRIBUTIONS
- Supporting Information
The present study compared the classification of RA using the 1987 ACR criteria and the 2010 ACR/EULAR criteria in a large cohort of patients with early arthritis. Use of the 2010 criteria classified more patients with RA than the 1987 criteria, and 11.3% of the patients with RA according to the 1987 criteria were not classified as having RA according to the 2010 criteria. A large proportion of the patients with early arthritis who developed RA according to the 1987 criteria during the disease course could, at first presentation, be classified as having RA according to the 2010 criteria. This denotes that the 2010 criteria have met the demand of classifying RA at an earlier phase of the disease compared with the 1987 criteria. Application of the 2010 classification also led to a revoked diagnosis at a later phase in 18% of patients (or 9.5%, depending on the studied population), substantiating the concerns with regard to an increase in heterogeneity with use of the 2010 criteria. Compared with the 1987 criteria, the sensitivity of the 2010 criteria was higher, but the specificity was lower.
In this study, several choices were made when applying the 2010 ACR/EULAR criteria. Initially, we omitted information on hand and feet radiographs, because a clear description of erosive disease resembling RA was not provided by Aletaha et al (2). We then repeated the analyses, defining a total Sharp/van der Heijde erosion score ≥2 as erosiveness. Fairly similar results were observed. This may suggest that evaluating radiographs in the early phase of arthritis is not highly relevant for the classification of RA. The number of erosive joints in patients with early arthritis was recently shown to be moderately predictive of the development of RA (7).
We used a swollen joint count in 66 joints and a tender joint count in 68 joints. In clinical practice, a 44- or 28-joint count is frequently used. To evaluate the effect of assessing different numbers of joints, we repeated the analyses with the lower joint counts. The number of patients classified as having RA decreased, but the test characteristics were only marginally affected.
This study has some limitations. First, it is based on a single inception cohort, and more studies are needed to establish the sensitivity and specificity of the new criteria. A complicating factor is the ambiguity regarding which outcome measure should be used as the gold standard in RA. This was subject to discussion within the working group that derived the 2010 criteria, and the outcome measure of initiation of MTX was chosen. This outcome may not be appropriate when studying chronologically older cohorts. For example, in the 1990s it was not common practice to start MTX early in a patient with arthritis of recent onset who did not fulfill the 1987 criteria. For this reason, we chose any DMARD therapy instead of MTX therapy as an outcome. For verification, we additionally used the persistence of arthritis over 5 years as an outcome. However, differences in the outcome measures may yield variations in the observed test characteristics.
All 3 of the outcome measures used here (initiation of MTX, initiation of any DMARD, and persistence of arthritis) are associated with the risk of misclassification, because these outcome measures can also be fulfilled in patients with other diagnoses, such as psoriatic arthritis. A diagnosis of psoriatic arthritis was also the most frequent cause of a revoked classification of RA at 1 year.
Another consideration is that 213 patients with early arthritis who were included in the EAC cohort after 2000 were used in the data-driven phase of development of the 2010 criteria (8). In the present study, we evaluated a considerably larger number of patients as well as 2 outcome measures in addition to MTX treatment. In order to determine whether this subset of patients affected the results, repeat analyses were performed in which these 213 patients were excluded. This repeat analysis did not yield substantially different results (data not shown). Nonetheless, validation of the 2010 criteria in other cohorts is required.
Given the emerging evidence on a “window of opportunity” (9) pointing to the need to provide treatment as early as possible, the question arises regarding what method best identifies individual patients with RA in an early phase. The investigators who developed the 2010 criteria emphasize that the new classification criteria were not developed as a diagnostic tool, and that a separate body of work is needed to develop such tools (2). Prediction rules aimed at early diagnosis have been developed and validated (10, 11). The question of what method is best to identify early RA on the individual patient level is still unanswered and is a subject for future studies.
In conclusion, the 2010 criteria for RA classify more patients with RA and do so at an earlier phase of disease. The discriminative ability of the 2010 ACR/EULAR criteria is reasonable, indicating that these criteria perform well to classify early RA.
- Top of page
- PATIENTS AND METHODS
- AUTHOR CONTRIBUTIONS
- Supporting Information
All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. Dr. van der Linden had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study conception and design. Van der Linden, Knevel, Huizinga, van der Helm-van Mil.
Acquisition of data. Van der Linden, Knevel, van der Helm-van Mil.
Analysis and interpretation of data. Van der Linden, Knevel, Huizinga, van der Helm-van Mil.