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Preventing the Progression From Undifferentiated Arthritis to Rheumatoid Arthritis: The Clinical and Economic Implications
Published Online: November 19, 2010
Michael H. Schiff, MD
The 2010 ACR/EULAR RA classification criteria can have a significant impact on the management of patients at the very early stages of disease. Although the authors clearly state that this classification system is not designed as a referral tool to help diagnose patients with RA, it is likely that the criteria will be incorporated into clinical practice as part of the overall diagnostic procedure. This can aid clinicians in identifying patients at early stages of RA who would benefit from therapeutic intervention and/or referral to a specialist. It is also possible that these criteria will be adopted by managed care organizations to determine the appropriateness of particular interventions for patients with early signs of RA. There are also economic benefits to limiting therapy to those who have a high probability of developing persistent RA while minimizing therapy for low-risk patients.
Screening Patients With UA at Risk for Progressing to RA
Screening patients who initially present with UA to identify those who are at a high probability of progressing to RA can be beneficial for the patient and the provider.
Serologic Factors
Serologic factors are a convenient and accurate measure to predict progression to RA. RF has been used for several decades and is the only serologic factor mentioned in the 1987 ACR criteria.7,13 More recently, several other biologic markers have been identified, including various ACPAs (tested as anti-cyclic citrullinated peptides [anti-CCPs]).14,15
To test the predictive value of ACPAs for progression to RA, van Gaalen and colleagues compared serologic assay results and disease progression in patients with UA.16 Of the 318 patients with UA, 69 were anti-CCP positive and 249 were anti-CCP negative at study entry. After 3 years, 93% of anti-CCP positive patients met the ACR criteria for RA, compared with 25% of anti-CCP negative patients (odds ratio, 37.8; 95% confidence interval [CI], 13.8-111.9) (Figure 1). The authors concluded that the presence of anti-CCP antibodies helps differentiate those patients with UA who are at risk for developing RA. The predictive value of RF and ACPA was further supported by a 4-year follow-up study of patients with undifferentiated polyarthritis.17
Although several different serologic markers can be used to screen patients with UA, studies have not definitively determined whether there are differences in predictive values associated with them. One study compared the predictive value of several of these markers, including RF and anti-CCPs.18 The results suggested that there were no significant differences in the predictive value of these serologic markers in distinguishing patients with UA who would later progress to RA. Furthermore, using a combination of serologic tests did not improve the predictive value, indicating that 1 assay is sufficient to make a determination.
Radiographic Criteria
In addition to serologic markers, researchers have attempted to identify other measures to predict progression from UA to RA. These include radiologic evaluation of baseline erosions in joints of the hands and feet, magnetic resonance imaging (MRI) of joints, or a combination of radiologic evaluation, serologic assays, and symptoms.19-22 Although these methods may prove effective in predicting which patients with UA may progress to RA, the inclusion of radiographic criteria, particularly MRI scans, can be prohibitive in terms of cost and time as a screening tool, and because an experienced musculoskeletal radiologist would be needed.
2010 ACR/EULAR RA Classification Criteria
The 2010 ACR/EULAR RA classification criteria provide a standardized algorithm for assessing patients with UA. These criteria will be important when developing inclusion criteria for clinical trials with patients in the very early stages of disease. They will also allow a comparison of patient cohorts from different clinical trials that adopt these criteria. Because these criteria use information regularly gathered at initial presentation in the clinic, assessment will not add to the time and cost of evaluation. Although these criteria are not meant to be used as a reference tool for diagnosis, they can be incorporated as part of the screening and diagnostic process for patients presenting with UA, and aid in the treatment decision-making process.
Benefits of Targeting Patients With UA for Active Treatment
Screening Patients With UA at Risk for Progressing to RA
Screening patients who initially present with UA to identify those who are at a high probability of progressing to RA can be beneficial for the patient and the provider.
Serologic Factors
Serologic factors are a convenient and accurate measure to predict progression to RA. RF has been used for several decades and is the only serologic factor mentioned in the 1987 ACR criteria.7,13 More recently, several other biologic markers have been identified, including various ACPAs (tested as anti-cyclic citrullinated peptides [anti-CCPs]).14,15
To test the predictive value of ACPAs for progression to RA, van Gaalen and colleagues compared serologic assay results and disease progression in patients with UA.16 Of the 318 patients with UA, 69 were anti-CCP positive and 249 were anti-CCP negative at study entry. After 3 years, 93% of anti-CCP positive patients met the ACR criteria for RA, compared with 25% of anti-CCP negative patients (odds ratio, 37.8; 95% confidence interval [CI], 13.8-111.9) (Figure 1). The authors concluded that the presence of anti-CCP antibodies helps differentiate those patients with UA who are at risk for developing RA. The predictive value of RF and ACPA was further supported by a 4-year follow-up study of patients with undifferentiated polyarthritis.17
Although several different serologic markers can be used to screen patients with UA, studies have not definitively determined whether there are differences in predictive values associated with them. One study compared the predictive value of several of these markers, including RF and anti-CCPs.18 The results suggested that there were no significant differences in the predictive value of these serologic markers in distinguishing patients with UA who would later progress to RA. Furthermore, using a combination of serologic tests did not improve the predictive value, indicating that 1 assay is sufficient to make a determination.
Radiographic Criteria
In addition to serologic markers, researchers have attempted to identify other measures to predict progression from UA to RA. These include radiologic evaluation of baseline erosions in joints of the hands and feet, magnetic resonance imaging (MRI) of joints, or a combination of radiologic evaluation, serologic assays, and symptoms.19-22 Although these methods may prove effective in predicting which patients with UA may progress to RA, the inclusion of radiographic criteria, particularly MRI scans, can be prohibitive in terms of cost and time as a screening tool, and because an experienced musculoskeletal radiologist would be needed.
2010 ACR/EULAR RA Classification Criteria
The 2010 ACR/EULAR RA classification criteria provide a standardized algorithm for assessing patients with UA. These criteria will be important when developing inclusion criteria for clinical trials with patients in the very early stages of disease. They will also allow a comparison of patient cohorts from different clinical trials that adopt these criteria. Because these criteria use information regularly gathered at initial presentation in the clinic, assessment will not add to the time and cost of evaluation. Although these criteria are not meant to be used as a reference tool for diagnosis, they can be incorporated as part of the screening and diagnostic process for patients presenting with UA, and aid in the treatment decision-making process.
Benefits of Targeting Patients With UA for Active Treatment
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