Do you know the possible risks of seropositive RA?
40%-60% OF RA PATIENTS
are positive for anti-CCP
and RF antibodies5
40%-60% OF RA
PATIENTS
are positive for
anti-CCP and RF
antibodies5
Anti-CCP+
patients
were ~2.6x more likely to have
ISCHEMIC
HEART DISEASE†
vs anti-CCP– patients
OR 2.58 (95% CI: 1.17-5.65) N=937
Study design: In a prospective cohort study in predominantly
seropositive RA patients (79.4% RF+ and 71.7% anti-CCP+), patients
were split into 2 cohorts: anti-CCP+ patients (n=672) and anti-CCP–
patients (n=265). Patients were evaluated to assess the relationship
between anti-CCP antibodies and cardiovascular disease.‡
Inclusion criteria: All patients met ACR criteria for RA.
Limitations6,7:
Observational in nature and used data from routine clinical practice
Patients were not randomized
Can only evaluate association and therefore unable
to determine causality
Anti-CCP+ patients
were ~2.6x more likely to have
ISCHEMIC
HEART DISEASE†
vs anti-CCP– patients
OR 2.58 (95% CI: 1.17-5.65)
N=937
Study design: In a prospective cohort study in predominantly
seropositive RA patients (79.4% RF+ and 71.7% anti-CCP+), patients
were split into 2 cohorts: anti-CCP+ patients (n=672) and anti-CCP–
patients (n=265). Patients were evaluated to assess the relationship
between anti-CCP antibodies and cardiovascular disease.‡
Inclusion criteria: All patients met ACR criteria for RA.
Limitations6,7:
Observational in nature and used data from routine clinical practice
Patients were not randomized
Can only evaluate association and therefore unable
to determine causality
ACR, American College of Rheumatology; anti-CCP, anti-cyclic citrullinated peptide; CV, cardiovascular; OR, odds ratio; RF, rheumatoid factor.
In a predominantly seropositive patient population,
RA patients with high disease activity were
more likely to experience major adverse cardiovascular events (MACE)8
Study design: In a prospective observational cohort study, researchers evaluated the association between RA disease activity and cardiovascular events among a predominantly seropositive (anti-CCP+ or RF+) population (74.2%).
Inclusion criteria: All patients met ACR criteria for RA, were 18 years or older, and had a baseline CDAI measured between October 2001 and May 2019.
Limitations6-8:
- Observational in nature and used data from routine clinical practice
- Patients were not randomized
- Can only evaluate association and therefore unable to determine causality
After 6 months of follow-up:
Patients with active RA and high disease activity§
were
nearly
~3x
as likely to
experience a
MACE||
vs RA patients in remission
HR 2.99 (95% CI: 1.48-6.02) N=18,399
The risk declined over time during the 5-year follow-up
period, with high, moderate, and low CDAI scores
having similar risk ratios at 5 years.
After 6 months of follow-up:
Patients with active RA and
high disease activity§
nearly
~3x
as likely to experience a
MACE||vs RA patients in remission
HR 2.99 (95% CI: 1.48-6.02)
N=18,399
The risk declined over time during the
5-year follow-up period, with high,
moderate, and low CDAI scores having
similar risk ratios at 5 years.
Study design: In a prospective observational cohort study, researchers evaluated the association between RA disease activity and cardiovascular events among a predominantly seropositive (anti-CCP+ or RF+) population (74.2%).
Inclusion criteria: All patients met ACR criteria for RA, were 18 years or older, and had a baseline CDAI measured between October 2001 and May 2019.
Limitations6-8:
- Observational in nature and used data from routine clinical practice
- Patients were not randomized
- Can only evaluate association and therefore unable to determine causality
Major comorbidities included hypertension (32%), hyperlipidemia (18.8%), diabetes (8.9%), and CVD (4.7%).
CDAI, Clinical Disease Activity Index; CVD, cardiovascular disease; HR, hazard ratio.
Consider proactively
screening for CV events and
caring for your patients with
these risks in mind
Anti-CCP+
patients
had ~3.4x the risk of
RA-RELATED ILD
and INTERSTITIAL
PULMONARY
FIBROSIS
vs anti-CCP– patients
HR 3.394 (95% CI: 1.675–6.879) N=710
Study design: This meta-analysis pooled 4 studies of anti-CCP– patients
(n=179) and anti-CCP+ patients (n=531) evaluating the relationship
between seropositivity and RA-related lung manifestations.
Inclusion criteria:
All patients were diagnosed with RA
Studies on RA-related pulmonary disease¶
Case-control or cohort studies
Studies with distributions of serum anti-CCP (positive or negative)
in patients with RA-related pulmonary disease and RA controlsStudies reporting basic participant characteristics
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
had ~3.4x the risk of
RA-RELATED ILD
and INTERSTITIAL
PULMONARY
FIBROSIS
vs anti-CCP– patients
HR 3.394 (95% CI: 1.675–6.879)
N=710
Study design: This meta-analysis pooled 4 studies of anti-CCP– patients
(n=179) and anti-CCP+ patients (n=531) evaluating the relationship
between seropositivity and RA-related lung manifestations.
Inclusion criteria:
All patients were diagnosed with RA
Studies on RA-related pulmonary disease¶
Case-control or cohort studies
Studies with distributions of serum anti-CCP (positive or negative)
in patients with RA-related pulmonary disease and RA controlsStudies reporting basic participant characteristics
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.
ILD, interstitial lung disease.
Are you screening for ILD?
Consider the impact of
seropositivity on your patients'
disease course
Anti-CCP+
patients
had a
72%
increased risk of
DEATH# vs anti-CCP– patients
OR 1.72 (95% CI: 1.01–2.91) N=937
The main causes of death included infections (32.2%),
tumors (24.7%), cardiovascular disease (18.2%), and
amyloidosis (10.7%).
Study design: In a prospective cohort study in predominantly
seropositive RA patients (79.4% RF+ and 71.7% anti-CCP+), patients
were split into 2 cohorts: anti-CCP+ patients (n=672) and anti-CCP–
patients (n=265). Patients were evaluated to assess the relationship
between anti-CCP antibodies and cardiovascular disease.
Inclusion criteria: All patients met ACR criteria for RA.
Limitations6,7:
Observational in nature and used data from routine clinical practice
Patients were not randomized
Can only evaluate association and therefore unable to determine
causality
Anti-CCP+ patients
had a 72%
increased risk of
DEATH# vs anti-CCP– patients
OR 1.72 (95% CI: 1.01–2.91)
N=937
The main causes of death included
infections (32.2%), tumors (24.7%),
cardiovascular disease (18.2%), and
amyloidosis (10.7%).
Study design: In a prospective cohort study in predominantly
seropositive RA patients (79.4% RF+ and 71.7% anti-CCP+), patients were split into 2 cohorts: anti-CCP+ patients (n=672) and anti-CCP–
patients (n=265). Patients were evaluated to assess the relationship
between anti-CCP antibodies and cardiovascular disease.
Inclusion criteria: All patients met ACR criteria for RA.
Limitations6,7:
Observational in nature and used data from routine clinical practice
Patients were not randomized
Can only evaluate association and therefore unable to determine causality
CV risk factors (smoking, overweight, diabetes, hyperlipidemia, hypertension) were present in these patients at the time of study entry.4
Consider the risks of
seropositivity from the start
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. 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
3. Zhu J, Zhou Y, Chen X, Li J. A metaanalysis of the increased risk of rheumatoid arthritis-related pulmonary disease as a result of serum anticitrullinated protein antibody positivity. J Rheumatol. 2014;41(7):1282-1289.
4. López-Longo FJ, Oliver-Miñarro D, de la Torre I, et al. Association between anti-cyclic citrullinated peptide antibodies and ischemic heart disease in patients with rheumatoid arthritis. Arthritis Rheum. 2009;61(4):419-424.
5. Niewold TB, Harrison MJ, Paget SA. Anti-CCP antibody testing as a diagnostic and prognostic tool in rheumatoid arthritis. Q J Med. 2007;100:193-201.
6. 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.
7. Hannan EL. Randomized clinical trials and observational studies: guidelines for assessing respective strengths and limitations. JACC Cardiovasc Interv. 2008;1(3):211-217.
8. Yoshida K, Harrold LR, Middaugh N, et al. Time-varying association of rheumatoid arthritis disease activity to subsequent cardiovascular risk. ACR Open Rheumatol. 2022;4(7):587-595.