Factors associated with progression to inflammatory arthritis in first-degree relatives of individuals with RA following autoantibody positive screening in a non-clinical setting

Affiliations

PMID: 32928740
DOI: 10.1136/annrheumdis-2020-217066

Abstract

Objectives: Little is known about the likelihood of developing inflammatory arthritis (IA) in individuals who screen autoantibody positive (aAb+) in a non-clinical research setting.

Methods: We screened for serum cyclic citrullinated peptide antibody (anti-CCP) and rheumatoid factor isotype aAbs in subjects who were at increased risk for rheumatoid arthritis (RA) because they are a first-degree relative of an individual with classified RA (n=1780). We evaluated combinations of aAbs and high titre aAbs, as defined by 2-times (2 x) the standard cut-off and an optimal cut-off, as predictors of our two outcomes, aAb+ persistence and incident IA.

Results: 304 subjects (17.1%) tested aAb+; of those, 131 were IA-free and had at least one follow-up visit. Sixty-four per cent of these tested aAb+ again on their next visit. Anti-CCP+ at levels ≥2 x the standard cut-off was associated with 13-fold higher likelihood of aAb +persistence. During a median of 4.4 years (IQR: 2.2-7.2), 20 subjects (15.3%) developed IA. Among subjects that screened anti-CCP+ at ≥ 2 x or ≥an optimal cut-off, 32% and 26% had developed IA within 5 years, respectively. Both anti-CCP cut-offs conferred an approximate fourfold increased risk of future IA (HR 4.09 and HR 3.95, p<0.01).

Conclusions: These findings support that aAb screening in a non-clinical setting can identify RA-related aAb+ individuals, as well as levels and combinations of aAbs that are associated with higher risk for future IA. Monitoring for the development of IA in aAb+ individuals and similar aAb testing approaches in at-risk populations may identify candidates for prevention studies in RA.

Keywords: ant-CCP; epidemiology; rheumatoid arthritis; rheumatoid factor; synovitis.

Conflict of interest statement

Competing interests: MKD reports grants from Pfizer, outside the submitted work; JHB reports grants from NIH, during the conduct of the study; in addition, JHB reports grants from Jannsen and from BMS, outside the submitted work; PKG reports grants from NIH, during the conduct of the study; KDD reports non-financial support from Inova Diagnostic, outside the submitted work; in addition, KDD has a patent on biomarkers in rheumatoid arthritis with royalties paid; VMH reports grants from NIH, a grant from Pfizer, and grants and personal fees from Janssen Research and Development and personal fees from Celgene, all outside of the submitted work. JMN reports a grant from Pfizer, outside the submitted work; in addition, JMN reports grants from NIH, during the conduct of the study.