Factors associated with progression to inflammatory arthritis in first-degree relatives of individuals with RA following autoantibody positive screening in a non-clinical setting. Issue 2 (14th September 2020)

• Record Type: Journal Article
• Authors: Bemis, Elizabeth A; Demoruelle, M Kristen; Seifert, Jennifer A; Polinski, Kristen J; Weisman, Michael H; Buckner, Jane H; Gregersen, Peter K; Mikuls, Ted R; ODell, James R; Keating, Richard M; Deane, Kevin D; Holers, V Michael; Norris, Jill M
• Is Part Of: Annals of the rheumatic diseases. Volume 80:Issue 2(2021)
• Page Start: 154
• Page End: 161
• Publication Date: 2020-09-14
• Subjects: rheumatoid arthritis -- synovitis -- ant-CCP -- rheumatoid factor -- epidemiology; Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2020-217066
• Languages: English
• ISSNs: 0003-4967

Abstract

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.