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Arthritis Care Res (Hoboken). 2018 Dec 20. doi: 10.1002/acr.23820. [Epub ahead of print]

Impact of Cyclic Citrullinated Peptide Antibody Level on Progression to Rheumatoid Arthritis in Clinically Tested CCP-Positive Patients Without RA.

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Department of Medicine, Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA.
Tufts University School of Medicine, Boston, MA.
Department of Medicine, Division of Rheumatology, University of Colorado, Denver, Aurora, CO.



We investigated risk of progression to rheumatoid arthritis (RA) in patients who were cyclic citrullinated antibody positive (CCP+) without RA at initial presentation.


We performed a retrospective cohort study of CCP+ individuals seen at a US tertiary care system between 2009-2018 who were without RA or other systemic rheumatic disease by medical record review at time of CCP positivity. Progression to classifiable RA was determined through medical record review. We investigated risk of progression to RA overall and stratified by CCP level (low: >1 to 2 times upper limit of normal [x ULN]; medium: >2 to 3x ULN; high: >3x ULN). Multivariable Cox regression estimated the hazard ratio (HR) and 95% confidence interval (95%CI) for RA by CCP level.


We identified 340 CCP+ patients who were without RA or other rheumatic disease at baseline. During 1047 person-years of follow-up, 73 (21.5%) patients developed RA. Risk of progression to RA increased with CCP level, with 46.0% (95%CI 34.7-55.3) of high level CCP patients progressing to RA by 5 years. Compared to low CCP, medium (HR 3.00, 95%CI 1.32-6.81) and high (HR 4.83, 95%CI 2.51-9.31) CCP levels were strongly associated with progression to RA, adjusting for age, sex, body mass index, smoking, family history of RA, and rheumatoid factor level.


Among CCP+ patients without RA, risk for progression to RA increased substantially with increasing CCP level. This study provides further support for close monitoring for development of RA among CCP+ patients and identifying strategies to mitigate this risk. This article is protected by copyright. All rights reserved.


cyclic citrullinated peptide antibody; prevention; rheumatoid arthritis

[Available on 2020-06-20]

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