What is the significance of anti-cyclic citrullinated peptide (anti-CCP) antibodies?

From the Guidelines

Anti-CCP is a highly specific test for rheumatoid arthritis, with a specificity of around 95-98%, making it a valuable diagnostic tool. The test detects antibodies against citrullinated proteins, which are commonly found in patients with rheumatoid arthritis (RA) 1. Anti-CCP antibodies often appear years before clinical symptoms develop, allowing for early diagnosis and intervention. The test is ordered when a patient presents with joint pain, swelling, morning stiffness, or other symptoms suggestive of RA, typically alongside other tests like rheumatoid factor (RF).

• A positive anti-CCP result strongly suggests RA, especially when clinical symptoms are present, while negative results don't completely rule out the disease.
• Higher antibody levels may indicate more aggressive disease and predict greater joint damage over time.
• This test helps clinicians distinguish RA from other inflammatory arthritis conditions and guides treatment decisions, as early intervention with disease-modifying antirheumatic drugs (DMARDs) can significantly improve outcomes by preventing irreversible joint damage 1. The pooled diagnostic odds ratio (DOR) of 43.05 (95% CI 32.00–57.93) is an unpaired measure of test effectiveness, indicating that a subject with the disease is 43.05 times more likely to test positive on the anti-CCP test than a subject without the disease is to test positive on the anti-CCP test 1.
• The positive and negative likelihood ratios (LR+ and LR−, respectively) indicate how much more likely (LR+) a patient who has a positive diagnosis according to the anti-CCP test is to be a True Positive than a False Positive (15.39 times more likely) and how much more likely (1/LR−) a patient who has a negative diagnosis according to the anti-CCP test is to be a True Negative than a False Negative (2.8 times more likely) 1. The use of anti-CCP testing is recommended as part of a comprehensive diagnostic approach to RA, particularly in patients with high-risk features such as autoantibody positivity, high disease activity, and early joint damage.

From the Research

Anti-CCP Antibodies

• Anti-CCP antibodies are used as a diagnostic and prognostic tool in rheumatoid arthritis, with high specificity and presence early in the disease process 2
• They can identify patients who are likely to have severe disease and irreversible damage, but a negative result does not exclude disease 2
• Anti-CCP antibodies are more specific than rheumatoid factor for detecting rheumatoid arthritis, and have not been found at a significant frequency in other diseases to date 2

Treatment of Rheumatoid Arthritis

• Combination therapy with methotrexate, sulfasalazine, and hydroxychloroquine is more effective than either methotrexate alone or a combination of sulfasalazine and hydroxychloroquine 3, 4, 5
• Methotrexate and sulfasalazine can also be used in combination with other DMARDs, and triple therapy regimens are effective 6, 5
• The triple combination of methotrexate, sulfasalazine, and hydroxychloroquine is well-tolerated and has superior efficacy to double combination therapies 5

Diagnostic Performance

• Anti-CCP antibody testing has high specificity, but low sensitivity, and a negative result does not exclude disease 2
• The presence of anti-CCP antibodies early in the disease process can help identify patients who are likely to have severe disease and irreversible damage 2