| Summary: | Objective: The events that occur prior to the onset of rheumatoid arthritis (RA) continue to be delineated. We examined the relationship between self-reported joint symptoms, functional disability, and anticitrullinated protein antibody (ACPA) status in a cohort of first-degree relatives (FDR) of patients with RA who are at risk of future disease development. Methods: We studied a cohort of 607 FDR of First Nations (FN) patients with RA who are at increased risk for future RA development, and analyzed data collected at their enrollment study visit. In parallel, we analyzed data from 279 FN participants with no family history of RA. A subset of FDR developed inflammatory arthritis and we analyzed longitudinal data in this group. Results: The prevalence of joint symptoms and functional disability was higher in FDR compared to non-FDR (all P < 0.001). Difficulty walking (37.3% vs 18.0%) and modified Health Assessment Questionnaire (mHAQ) results were higher in ACPA-positive FDR compared to ACPA-negative FDR, and mHAQ was independently associated with ACPA seropositivity (OR 2.79, 95% CI 1.56 -5.00). Longitudinally, in individuals who developed ACPA-positive RA, ACPA level and mHAQ score were significantly associated (R = 0.45, P < 0.001) in the preclinical period. Conclusion: Compared to population-based controls, FDR have a high burden of joint symptoms and functional disability. Functional disability was most closely associated with ACPA seropositivity in the FDR, suggesting a direct role for ACPA outside of the context of clinically detectable synovitis. HAQ appears to be particularly valuable in the assessment of individuals at risk for future RA development.
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