Abstract
This systematic review assesses the current status of anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF) tests in the diagnosis and prognosis of rheumatoid arthritis (RA). We reviewed publications on tests and biomarkers for early diagnosis of RA from English-language MEDLINE-indexed journals and non-MEDLINE-indexed sources. 85 publications were identified and reviewed, including 68 studies from MEDLINE and 17 non-MEDLINE sources. Anti-CCP2 assays provide improved sensitivity over anti-CCP assays and RF, but anti-CCP2 and RF assays in combination demonstrate a positive predictive value (PPV) nearing 100%, greater than the PPV of either of the tests alone. The combination also appears to be able to distinguish between patients whose disease course is expected to be more severe and both tests are incorporated in the 2010 ACR Rheumatoid Arthritis Classification Criteria. While the clinical value of anti-CCP tests has been established, differences in cut-off values, sensitivities and specificities exist between first-, second- and third-generation tests and harmonization efforts are under way. Anti-CCP and RF are clinically valuable biomarkers for the diagnosis and prognosis of RA patients. The combination of the two biomarkers in conjunction with other clinical measures is an important tool for the diagnosis and management of RA patients.
Highlights
Rheumatoid arthritis (RA), the most commonly occurring form of inflammatory polyarthritis, is prevalent in approximately 0.8% of adults worldwide [1]
We identified 68 articles from MEDLINE pertaining to current diagnostic guidelines and practices for RA, and to anti-CCP and rheumatoid factor (RF) as diagnostic tests for RA
The recent addition of Anticitrullinated Protein Antigens (ACPAs) testing in the American College of Rheumatology (ACR)’s updated 2010 RA classification criteria is an acknowledgment of the clinical value of these biomarkers for the diagnosis of RA patients [97]
Summary
Rheumatoid arthritis (RA), the most commonly occurring form of inflammatory polyarthritis, is prevalent in approximately 0.8% of adults worldwide [1]. 20%–30% of RA patients become so severely debilitated within the first three years following initial diagnosis that they become permanently disabled [1]. Treatment options for RA patients have improved dramatically. Recent evidence indicates that early introduction of methotrexate (MTX) therapy in undifferentiated arthritis (UA) patients seropositive for anti-CCP delays differentiation to RA and retards the progression of joint destruction [4]. Initiation of treatment without a confirmed diagnosis of RA is inappropriate for at least half of patients with UA [5], as therapies are potentially toxic and costly
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