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Reviews6 April 2010

Systematic Review: Accuracy of Anti–Citrullinated Peptide Antibodies for Diagnosing Rheumatoid Arthritis

    Author, Article, and Disclosure Information
    https://doi.org/10.7326/0003-4819-152-7-201004060-00010
    Background:

    Early recognition and treatment of rheumatoid arthritis is important to prevent irreversible joint damage. Anti–citrullinated peptide antibodies (ACPA) have been suggested for early diagnosis.

    Purpose:

    To compare the accuracy of ACPA and rheumatoid factor in diagnosing rheumatoid arthritis in patients with early symptoms of the disease.

    Data Sources:

    10 medical databases from inception to September 2009, with no language or publication restrictions, and references of included studies.

    Study Selection:

    Two independent reviewers screened searches. Full articles were assessed by one reviewer and checked by a second reviewer to identify studies that reported 2 × 2 data on ACPA for the diagnosis of rheumatoid arthritis (by 1987 American College of Rheumatology criteria).

    Data Extraction:

    One reviewer abstracted data on patient characteristics, ACPA details, and 2 × 2 data and assessed study quality by using the QUADAS tool. A second reviewer checked extractions.

    Data Synthesis:

    151 studies were included, with considerable heterogeneity in sensitivity (range, 12% to 93%) and specificity (range, 63% to 100%). In cohort studies that investigated second-generation anti–cyclic citrullinated peptide antibodies (anti-CCP2) in patients with early rheumatoid arthritis (<2 years), summary sensitivity and specificity were 57% (95% CI, 51% to 63%) and 96% (CI, 93% to 97%), respectively. Case–control and cross-sectional studies and studies of patients with established rheumatoid arthritis all overestimated sensitivity. Anti-CCP2 had greater specificity than rheumatoid factor (96% vs. 86%), with similar sensitivity. Evidence was insufficient to ascertain whether the combination of anti-CCP2 and rheumatoid factor provides additional benefit over anti-CCP2 alone.

    Limitations:

    Most studies used a diagnostic case–control design, which overestimated sensitivity. Items relating to study quality were rarely reported. Publication bias could not be assessed.

    Conclusion:

    Anti-CCP2 should be included in the work-up of patients with early symptoms of rheumatoid arthritis.

    Primary Funding Source:

    United Kingdom Medical Research Council.

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