New Criteria May Better Classify Early Rheumatoid Arthritis

Newswise — Changing the way in which rheumatoid arthritis is diagnosed by including one new assessment and excluding two current assessments may allow for the identification and inclusion of a larger number of patients with early disease in clinical studies, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Boston.

The current classification criteria for RA are quite sensitive for patients with established disease. These criteria are primarily used for determining whether a patient qualifies to be included in a study of RA but are often used by clinicians for diagnostic purposes. Some of the current clinical and radiological findings in the RA criteria may not appear until the disease has been present for some time, and thus may not be as useful to classify or diagnose early RA. As the approach to managing rheumatoid arthritis shifts to treating patients earlier in the course of their disease, before joint damage and disability has begun, it is important to correctly identify patients with early disease, so that they can be included in assessments of new therapies.

Investigators set out to assess the impact of including anti-CCP testing and excluding rheumatoid nodules and radiographic changes on the classification of early rheumatoid arthritis. To do so, they identified 391 subjects seen in the Arthritis Center of Brigham and Women's Hospital who were tested for both rheumatoid factor and antibodies to cyclic citrullinated peptide (anti-CCP) on the same day between January 1 and June 1, 2004. Based on analysis of these patients' electronic medical records, 99 patients were excluded and the records of 292 subjects were ultimately analyzed.

The average age of subjects was 54 years old; 82 percent of them were women, and the average duration of symptoms was just over four years. Seventeen percent of these patients had a positive rheumatoid factor, and 14 percent tested positive for anti-CCP at initial testing. By including anti-CCP testing and excluding rheumatoid nodules and radiographic changes, the number of patients correctly classified as having RA jumped from 51 percent to 74 percent. Applying these criteria sets to patients who have had symptoms for less than six months (when signs such as nodules and radiographic changes may not yet be apparent) demonstrated an even greater relative increase in the number of patients appropriately classified as having RA: from 25 to 63 percent.

"Anti-CCP testing is now widely used in clinical practice to aid in the diagnosis of RA, but is not included in the current ACR criteria for the classification of RA. Additionally, RA therapies available today are able to slow or halt disease progression. It is important that new therapies are tested early in the disease course before significant damage has occurred," said Katherine P. Liao, MD, Brigham and Women's Hospital, Boston, Mass., and lead investigator in the study. "The current criteria for RA diagnosis include elements that may not become apparent until later in the disease. Minor modifications in these criteria may allow us to correctly identify RA patients earlier, when intervention may be more effective."

The American College of Rheumatology is the professional organization of and for rheumatologists and health professionals who share a dedication to healing, preventing disability and curing arthritis and related rheumatic and musculoskeletal diseases. For more information on the ACR's annual meeting, see http://www.rheumatology.org/annual.

Editor's Notes: Dr. Liao will present this research during the ACR Annual Scientific Meeting at the Boston Convention and Exhibition Center from 4:30 " 6:00 pm ET on Saturday, November 10, 2007, in Grand Ballroom East. Presentation Number: 2150

Anti-CCP-Modified Criteria for the Classification of Early Rheumatoid Arthritis

Katherine P. Liao, Kerri L. Batra, Lori Chibnik, Anne H. Fossel, Peter H. Schur, Karen H. Costenbader. Brigham and Women's Hospital, Boston, MA

PURPOSE: To assess the effect of including antibodies to cyclic citrullinated peptide (anti-CCP) on the performance characteristics of the current ACR criteria (Arnett F, Arthritis Rheum, 1988) for classifying RA.

METHODS: We identified all outpatients seen in the Arthritis Center of our academic medical center with both rheumatoid factor (RF) and anti-CCP tested on the same day between January 1, 2004 and June 1, 2004. We reviewed their electronic medical records for ACR criteria, treating rheumatologist diagnoses in follow-up, and results of RF and anti-CCP testing. We revised the existing ACR criteria in two ways: (1) by adding the results of anti-CCP testing, and (2) by removing rheumatoid nodules and radiographic changes (erosions) (Table 1). We compared the sensitivity and specificity of the ACR criteria to our two sets of modified criteria and compared these to the rheumatologists' diagnoses at the most recent follow-up visit.

RESULTS: 391 subjects were identified and their electronic medical records were reviewed. 99 subjects were excluded, 20 with juvenile RA and 79 with no follow-up visit. Thus, 292 subjects were included in this analysis. Mean age of subjects was 52.3; 83% were women, and the mean duration of symptoms was 4.1 years. 17% of patients were RF+ and 14% were anti-CCP+ at initial testing. 78 (27%) had definite RA per their rheumatologists at the most recent follow-up.

For all subjects, the Anti-CCP Revised Criteria increased sensitivity for the classification of RA from 51% to 55%. This was also true for subjects with symptoms < 6 months (n=79), for whom the sensitivity increased from 25% to 49%. For subjects with symptoms < 6 months, using the Early RA Revised Criteria increased sensitivity from 25% to 63% with an acceptable decrease in specificity to 65% (Table 2).

CONCLUSION: Current clinical trials aim to include subjects with early RA to test whether disease progression can be halted in its early stages. Including anti-CCP and excluding rheumatoid nodules and radiographic changes increases the sensitivity of the ACR criteria, particularly for patients with symptoms < 6 months, and would allow for identification and inclusion of a larger number of patients with early RA in clinical studies.

Table 1. Criteria sets ACR Criteria Anti-CCP Revised Criteria Early RA Revised Criteria1. morning stiffness > 1 hr* x x x2. arthritis ≥ 3 joints* x x x3. hand arthritis* x x x4. symmetric arthritis* x x x5. rheumatoid nodules x x 6. RF x x x7. radiographic changes x x 8. anti-CCP x x# criteria needed ≥4 out of 7 ≥4 out of 8 ≥3 out of 6* Symptoms > 6 weeks

[Table 2, Performance Characteristics of Criteria for Classification of RA, available on request.]

Disclosure Block: K.P. Liao, None; K.L. Batra, None; L. Chibnik, None; A.H. Fossel, None; P.H. Schur, None; K.H. Costenbader, None.