Rheumatoid arthritis

Utility of testing for third-generation anticyclic citrullinated peptide (anti-CCP3) antibodies in individuals who present with new musculoskeletal symptoms but have a negative second-generation anticyclic citrullinated peptide (anti-CCP2) antibody test

RMD OpenPublished Prospective cohort study

Authors' conclusion

Anti-CCP3 testing could improve the prediction of IA development in anti-CCP2- individuals with new MSK symptoms.

Study context

Population
Individuals with new musculoskeletal (MSK) symptoms and a negative anti-CCP2 test
Participants
469 individuals
Exposure
Anti-CCP3 positive vs anti-CCP3 negative in anti-CCP2- individuals
  • Anti-CCP3 positiven = 16
Outcome
Progression to inflammatory arthritis (IA)
Follow-up
12 months
Methodological detailsunivariable and multivariable analyses
  • Univariable and multivariable analyses

Main finding

As reported in the abstract

Anti-CCP3 positive among anti-CCP2- individuals
16/469 (3.4%)
Anti-CCP3 positive individuals who developed inflammatory arthritis (IA)
4
Univariable: anti-CCP3 positivity associated with self-reported progression
p<0.01
Univariable: anti-CCP3 positivity associated with IA
p=0.03
Anti-CCP3 levels differed between progressors and non-progressors, all three categories
p<0.01
OR for progression at manufacturer's cut-off, rheumatoid arthritis (RA)
2.4 (95% CI 0.5 to 18.6)
OR for progression at manufacturer's cut-off, self-reported progression
7.5 (95% CI 2.3 to 24.0)
Multivariable: positivity at manufacturer's cut-off not associated with IA progression; ≥5 units cut-off associated with RA diagnosis
p=0.02

Observational data: associations, not effects.

Further findings

Prevalence of anti-CCP3 positivity · baseline

Positive anti-CCP3 test among anti-CCP2- individuals
16/469 (3.4%)

Self-reported and confirmed progression · 12 months

Self-reported IA
61/469 (13.0%)
Progression confirmed
43/61 (70.5%)
Diagnosis of IA
30/43 (69.8%)
Diagnosis of RA
13/43 (30.2%)

Multivariable analysis

Lower cut-off (≥5 units) associated with diagnosis of RA
P = 0.02
Anti-CCP3 positivity at manufacturer's cut-off did not remain associated with IA progression
  • Multivariable analysis

Original publication

Utility of testing for third-generation anticyclic citrullinated peptide (anti-CCP3) antibodies in individuals who present with new musculoskeletal symptoms but have a negative second-generation anticyclic citrullinated peptide (anti-CCP2) antibody test. RMD Open. Published 10 April 2024. doi:10.1136/rmdopen-2023-003927

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