#146 Anti-CCP: A truly helpful Rheumatoid Arthritis lab test?

CLINICAL QUESTION

QUESTION CLINIQUE

For Adult Rheumatoid Arthritis (RA), what is the diagnostic utility of Anti-Cyclic Citrullinated Protein antibodies (Anti-CCP)?

BOTTOM LINE

RÉSULTAT FINAL

Anti-CCP, with ~96% specificity and ~14 positive likelihood ratio, is good for assisting with the diagnosis of RA. Anti-CCP is present in only ¼ to ½ of patients before or at diagnosis, so a negative test does NOT rule out RA. It can also predict more aggressive joint erosion.

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EVIDENCE

DONNÉES PROBANTES

Seven systematic reviews^1-7 of Anti-CCP in adult RA, with 27-151 observational studies. Pooled results:
- Sensitivity and specificity^2-4,7 were 53%-71% and 95-96%, respectively.
- Likelihood ratios:^3,4 Positive likelihood ratio 12.5-15.9 and negative 0.36-0.42.
- Focusing on higher-level studies (diagnostic cohort) with an undifferentiated arthritis presentation: sensitivity generally lower (~54%) but specificity similar.⁴
Interpretation: Positive Anti-CCP means RA likely but a negative does NOT rule out RA.
Concerns (although study quality did not seem to impact findings⁷):
- Minority of studies well-designed: Cohorts of early, undifferentiated patients with prolonged follow-up by blinded study personnel.⁴
- Significant heterogeneity: Different control population,⁴ study designs,⁴ test cut-offs,^2,6 and laboratory standardizations.^2,6

Context:

Positive Anti-CCP also predicts joint erosion in RA, Odds Ratio 4.4 (95% Confidence Interval 3.6-5.3).⁸
How common is Anti-CCP:
- In RA patients?²
  - 23% early in symptoms.
  - ~50% at diagnosis.
  - ~53-70% at two years after diagnosis.
- Other populations?²
  - ≤1.5% in healthy populations.
  - ≤10% in other rheumatic disease (from lupus to psoriatic arthritis), except palindromic which is similar to RA.
    - Perhaps higher in some if erosive joint disease present.⁹
Rheumatoid Factor has a similar sensitivity but worse specificity.³
- Specificity: Anti-CCP=95% and Rheumatoid Factor=85%.
  - Positive likelihood ratios are 12.5 versus 4.9, respectively.
- Interpretation: Positive Anti-CCP > positive Rheumatoid Factor for making an RA diagnosis.
In Juvenile RA, Anti-CCP has a similar specificity (99%) but considerably worse sensitivity (10%): Anti-CCP is commonly negative, which does not rule out RA.10
RA diagnostic criteria: As well as joint involvement and acute phase reactants (ESR or C-Reactive Protein), Anti-CCP and Rheumatoid Factor are RA serology markers.¹¹
- Note: Anti-CCP is sometimes called ACPA (Anti-Citrullinated Protein Antibody).