New ACR/EULAR Classification Criteria May Identify Rheumatoid Arthritis In At-Risk People Prior to Clinical Presentation

Rheumatoid arthritis researchers are using the 2010 ACR/EULAR Rheumatoid Arthritis Classification Criteria in hopes of improving the ability to identify people with the RA even before they’re diagnosed with the disease in a clinical health care setting. They presented their findings this week at the American College of Rheumatology Annual Scientific Meeting in Atlanta.

Rheumatoid arthritis is a chronic disease that causes pain, stiffness, swelling, and limitation in the motion and function of multiple joints. Though joints are the principal body parts affected by RA, inflammation can develop in other organs as well. An estimated 1.3 million Americans have RA, and the disease typically affects women twice as often as men.

Classification criteria are the standard and accepted means by which researchers study and define a disease.

They allow researchers to classify individuals as having or not having a given disease, helping to standardize recruitment into clinical trials and other research studies. Although not intended as criteria for diagnosis in clinical practice, with some additional research, classification criteria may be modified and adopted for such use. Patients to whom these RA criteria should be applied must have confirmed presence of joint swelling, indicating synovitis - the inflammation of the synovial membrane, which lines a joint - in at least one joint, and should have no other possible diagnosis that might better explain the symptoms (such as lupus or gout).

Researchers recently applied the criteria to undiagnosed participants at potentially higher risk for RA based on family and genetic risk factors. The ongoing study involves a group of 1,790 participants who are being evaluated in several different ways - including evaluation of symptoms, joint examinations, and biomarker assessments - to determine the relationship between these factors, the new RA criteria, and the course of disease over the long-term.

The researchers found 21 previously undiagnosed participants with “definite RA,” including 17 females with an average age of nearly 49 years. Six (28.6 percent) of these 21 participants were positive for rheumatoid factor, one (4.8 percent) was positive for anti-cyclic citrullinated peptide antibody - which are autoantibodies (antibodies directed against one or more of an individual’s own proteins) that are frequently detected in the blood of people with RA - and 11 (52.4 percent) had elevated levels of C-reactive protein (indicating the presence of inflammation, which could be due to RA). The median number of joints swollen was three and tender joints was 11.

Jason R. Kolfenbach, MD - lead investigator in the study and an assistant professor at the University of Colorado School of Medicine, Division of Rheumatology - says the study’s findings may indicate an earlier phase of RA development than observed in people who are seeking diagnosis and care from a health care professional. “These were a group of subjects that had features of early arthritis,” Dr. Kolfenbach says of the participants in the study. “What will be interesting is following these subjects in order to see if they develop persistent findings that most of us would consider to be consistent with RA. Just defining them as early arthritis isn’t as good as following them over time to see if they develop more of the features that we typically see in chronic disease.”

“This is the first study of its kind, and like any first study it needs to be followed up and the findings replicated,” says V. Michael Holers, MD; the senior author of the study and a professor of medicine at the University of Colorado School of Medicine, Division of Rheumatology. “However, we’re certainly excited about the results and think that these new criteria might also be an excellent research tool to identify individuals who may be at high risk of progressing further in the disease course to a clinical diagnosis of RA.”

The identification of these subjects in a research, rather than clinical, setting may allow researchers to study and earlier phase of RA than is usually found in a clinical health care setting. Dr. Holers adds, “It’s too early to draw clinical or treatment inferences from this study, but we are very interested in closely following these individuals. If we can, in the future, confirm that this kind of screening test or related biomarker analysis is predictive of developing clinically-diagnosed RA, then we’ll be quite interested to address the question of clinical and therapeutic relevance again.”

The American College of Rheumatology is an international professional medical society that represents more than 8,000 rheumatologists and rheumatology health professionals around the world. Its mission is to advance rheumatology. The ACR/ARHP Annual Scientific Meeting is the premier meeting in rheumatology. For more information about the meeting, visit Follow the meeting on twitter by using the official hashtag: #ACR2010.

Editor’s Notes: Jason R. Kolfenbach, MD will present this research during the ACR Annual Scientific Meeting at the Georgia World Congress Center at 2:30 PM on Monday, November 8 in the Sidney J. Marcus Auditorium. Dr. Holers will be available for media questions and briefing at 8:30 AM on Monday, November 8 in the on-site press conference room, B 212.

Learn more about living well with rheumatic disease as well as rheumatologists and the role they play in health care. Also, discover how the ACR Research and Education Foundation’s Within Our Reach: Finding a Cure for Rheumatoid Arthritis campaign is accelerating RA research.

Presentation Number: 658

Application of the New ACR/EULAR Classification Criteria for Rheumatoid Arthritis to At-Risk Populations May Identify RA Prior to Clinical Presentation.

Jason R Kolfenbach, MD (Division of Rheumatology, University of Colorado Denver, Aurora, CO)
Lezlie Derber (Division of Rheumatology, University of Colorado Denver)
Kevin D Deane, MD (Division of Rheumatology, Division of Rheumatology, University of Colorado Denver, Aurora, CO)
Jan Hughes-Austin (Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver)
Michael H Weisman, MD (Rheumatology, Cedars Sinai Medical Center, Los Angeles, CA)
Jane Buckner (Benaroya Research Institute at Virginia Mason)
Ted R Mikuls, MD (Internal Medicine, University of Nebraska Medical Center, Omaha, NE)
James R O’Dell, MD (Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE)
Peter K Gregersen, MD (Biology & Human Genetics, N Shore Univ Hosp Rsch Ctr, Manhasset, NY)
Richard M Keating (institution, location)
Jill Norris, MPH, PhD (Biology & Human Genetics, N Shore Univ Hosp Rsch Ctr, Manhasset, NY)
V Michael Holers, MD (Epidemiology, University of Colorado Denver, Aurora, CO)

Objective: The proposed ACR/EULAR classification criteria were developed in part to identify early RA. Applying the new criteria to at-risk populations prior to evaluation in the health care setting may identify a unique cohort in which to study the evolution of very early symptomatic RA. We have established prospective cohorts of subjects at potentially higher risk for RA based on genetic risk factors as part of the SERA study (Studies of the Etiology of RA). The purpose of the current analysis was to identify and characterize a cohort within these populations with ‘definite RA’ according to the newly proposed criteria.

Methods: We have established a cohort of first-degree relatives (FDRs) of probands with RA. FDRs without RA by the 1987 ACR criteria undergo a joint exam and have laboratory data obtained. Identical data is collected on a second at-risk DR4-enriched population containing parents of children with high risk HLA alleles and/or Type I diabetes. The proposed RA criteria were applied to subjects in these cohorts with swelling suggestive of synovitis in ≥ 1 joint on clinical exam after exclusion of findings attributed to alternative diagnoses (e.g. trauma, osteoarthritis). Data regarding joint distribution, duration of symptoms, antibody status and presence of elevated inflammatory markers were used to apply the new criteria. Descriptive statistics were calculated for the identified cases.

Results: 1790 subjects were available for analysis. 153 subjects (8.5%) had synovitis in ≥ 1 joint on clinical exam. 21 subjects (1.17%) had ‘definite RA’ according to the proposed algorithm. 17/21 (81%) subjects were female with a mean age of 48.9 years old. 6/21 subjects (28.6%) were positive for rheumatoid factor (RF), one (4.8%) was positive for anti-cyclic citrullinated peptide antibody, and 11 (52.4%) had elevated levels of CRP. Median swollen and tender joint counts were 3 and 11, respectively. The average total score in the 21 subjects was 6.76. The mean scores for joint involvement, serology, acute phase reactant and duration were 4.33, 0.9, 0.52 and 1.0, respectively (Table 1).

Conclusion: Individuals with ‘definite RA’ according to the new criteria can be identified in these unique at-risk populations. A score ≥ 6 was driven primarily by joint involvement with the majority stemming from tender rather than swollen joints, a finding which may indicate an earlier phase of RA development than individuals presenting for clinical care. The identification of these subjects in a research rather than clinical setting may allow us to study an earlier phase of RA than possible in usual clinical practice. These subjects will be followed prospectively with multiple modalities including serial joint evaluations and biomarker assessments to evaluate the relationship between the new RA criteria and the longer-term evolution of RA.

Disclosure: Jason Kolfenbach, nothing to disclose; Lezlie Derber, nothing to disclose; Kevin Deane, nothing to disclose; Jan Hughes-Austin, nothing to disclose; Michael Weisman, nothing to disclose, Jane Buckner, nothing to disclose; Ted Mikuls, nothing to disclose; James O’Dell, nothing to disclose; Peter Gregersen, nothing to disclose; Richard Keating, nothing to disclose; Jill Norris, nothing to disclose; V Michael Holers, nothing to disclose.


Source:  American College of Rheumatology (ACR)

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