In a systematic review and meta-analysis of 10 studies:
Anti-CCP+
patients
RISK OF JOINT
EROSION
INCREASES
4-FOLD1
OR: 4.38 (95% CI: 5.34–3.59) N=3065
Study design: 10 studies of anti-CCP+ patients (n=2075) and anti-CCP– patients (n=990) were pulled in a systematic review and meta-analysis that assessed the prognostic value of anti-CCP seropositivity.
Limitations: Study selection and publication biases are potential limitations associated with meta-analyses. Heterogeneity of studies that include different patient populations, interventions, types of endpoints, and clinical protocols may lead to unreliability of the conclusion.
Anti-CCP+ patients
In a systematic review
and meta-analysis of
10 studies:
RISK OF JOINT
EROSION
INCREASES
4-FOLD1
OR: 4.38 (95% CI: 5.34–3.59)
N=3065
Study design: 10 studies of anti-CCP+ patients (n=2075) and anti-CCP– patients (n=990) were pulled in a systematic review and meta-analysis that assessed the prognostic value of anti-CCP seropositivity.
Limitations: Study selection and publication biases are potential limitations associated with meta-analyses. Heterogeneity of studies that include different patient populations, interventions, types of endpoints, and clinical protocols may lead to unreliability of the conclusion.
Meta-analysis that assessed
association between anti-CCP+
status and likelihood of
developing
joint erosions in patients with RA1
Anti-CCP+ patients had 4.382 times greater
odds of
developing joint erosions than anti-
CCP– patients.
See study design and limitations above
Study design: A cohort study of patients in the Veterans Affairs Rheumatoid Arthritis registry analyzed the relationship between disease activity and autoantibody status between 2 groups of patients: dual-seropositive (anti-CCP+/RF+) (n=1031) and double-negative (anti-CCP–/RF–) (n=204).
Limitation: This study examined an older, predominantly male patient population and did not evaluate radiographic outcomes. There were significant differences across autoantibody groups in age of diagnosis, disease duration, the presence of nodules, and methotrexate use. Methodology may not have fully eliminated the potential of erroneously elevated signals.
In a separate cohort,
registry study3:
Anti-CCP+
patients
were associated with
HIGHER
DISEASE
ACTIVITY
vs dual-seronegative (anti-CCP–/RF–)
patients or those with either
autoantibody alone
N=1488
Anti-CCP+ patients
In a separate cohort,
registry study3:
were associated with
HIGHER
DISEASE
ACTIVITY
vs dual-seronegative (anti-CCP–/RF–)
patients or those with either autoantibody alone
N=1488
Study design: A cohort study of patients in the Veterans Affairs Rheumatoid Arthritis registry analyzed the relationship between disease activity and autoantibody status between 2 groups of patients: dual-seropositive (anti-CCP+/RF+) (n=1031) and double-negative (anti-CCP–/RF–) (n=204).
Limitation: This study examined an older, predominantly male patient population and did not evaluate radiographic outcomes. There were significant differences across autoantibody groups in age of diagnosis, disease duration, the presence of nodules, and methotrexate use. Methodology may not have fully eliminated the potential of erroneously elevated signals.
vs a control population matched by age, sex, and ethnicity.4
Study design: This 24-month, prospective study investigated the
relationship between anti-CCP seropositivity and changes in
bone mineral density.
Inclusion criteria:
Treatment naïve
RA symptoms <12 months
Met 2010 ACR/EULAR criteria for RA
Had RA treatment for 24 months with low disease activity
(DAS28-CRP <3.2)*
Exclusion criteria: Patients with definitive diagnoses other than RA or
any suspicion of spondyloarthritis
Limitations5,6:
Observational in nature and used data from routine clinical practice
Patients were not randomized
Can only evaluate association and therefore unable to determine
causalityRelatively small sample size
vs a control population matched by age, sex, and ethnicity.4
Study design: This 24-month, prospective
study investigated the relationship between
anti-CCP seropositivity and changes in
bone mineral density.
Inclusion criteria:
Treatment naïve
RA symptoms <12 months
Met 2010 ACR/EULAR criteria for RA
Had RA treatment for 24 months with
low disease activity (DAS28-CRP <3.2)*
Exclusion criteria: Patients with definitive diagnoses other than RA or any suspicion of spondyloarthritis
Limitations5,6:
Observational in nature and used data
from routine clinical practicePatients were not randomized
Can only evaluate association and
therefore unable to determine causalityRelatively small sample size
ACR, American College of Rheumatology; anti-CCP, anti-cyclic citrullinated peptide; CRP, C-reactive protein; DAS, Disease Activity Score; EULAR, European Alliance of Associations for Rheumatology; RF, rheumatoid factor.
Consider the risks your
seropositive
patients may
be facing
References:
1. Jilani AA, Mackworth-Young CG. The role of citrullinated protein antibodies in predicting erosive disease in rheumatoid arthritis: a systematic literature review and metaanalysis. Int J Rheumatol. 2015;2015:728610. doi:10.1155/2015/728610
2. Smolen JS, Aletaha D, Barton A, et al. Rheumatoid arthritis. Nat Rev Dis Primers. 2018;4:18001. doi:10.1038/nrdp.2018.1
3. Sokolove J, Johnson DS, Lahey LJ, et al. Rheumatoid factor as a potentiator of anti-citrullinated protein antibody-mediated inflammation in rheumatoid arthritis. Arthritis Rheumatol. 2014;66(4):813-821. doi:10.1002/art.38307
4. Bugatti S, Bogliolo L, Manzo A, et al. Impact of anti-citrullinated protein antibodies on progressive systemic bone mineral density loss in patients with early rheumatoid arthritis after two years of treat-to-target. Front Immunol. 2021;12:710922. doi:10.3389.fimmu.2021/701922
5. Garrison LP Jr, Neumann PJ, Erickson P, Marshall D, Mullins CD. Using real-world data for coverage and payment decisions: the ISPOR Real-World Data Task Force report. Value Health. 2007;10(5):326-335.
6. Hannan EL. Randomized clinical trials and observational studies: guidelines for assessing respective strengths and limitations. JACC Cardiovasc Interv. 2008;1(3):211-217.