Pos0092 the Short- And Long-Term Risk of Developing Reumatoid Arthritis in Individuals Tested for Autoantibodies

Background: A proportion of healthy individuals express positivity for rheumatoid arthritis (RA)-related autoantibodies without clinically apparent RA 1, 2. Current research indicates that these individuals are at higher risk of subsequently developing manifest RA 3. Early diagnosis of RA and initiation of treatment has been shown to improve disease outcomes. Currently, there are no clinical guidelines on how and for how long these individuals should be monitored to detect and initiate early treatment of RA. Objectives: To estimate the short- and long-term risk of developing RA in autoantibody double- and single-positive individuals compared to autoantibody-negative individuals. Methods: All Danish individuals tested for RA-related autoantibodies, i.e., anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factors (RF): RF-IgM, RF-IgA, RF-IgG, from 1 January 2006 to 31 December 2021 in Denmark were identified. The two exposure groups were defined according to the presence of either: 1) single positivity (anti-CCP or RF), or 2) double positivity (anti-CCP and RF). The comparator group consisted of individuals with a negative test for all autoantibodies. Outcome was a registered RA-diagnosis in the Danish Rheumatology Quality Register (DANBIO) where all newly diagnosed Danish patients with RA have been registered since 2006. Crude and age and sex stratified incidence rates (IRs, per 1000 person years) of RA were calculated for the seropositive and seronegative groups. Cumulative incidence of RA was presented for all groups using the Aalen-Johansen estimator. Cause-specific cox regression was used to calculate hazard ratios (HR) with 95% confidence intervals (95% CI) for RA in both double-positive and single-positive groups compared with the seronegative. Results: A total of 6,696 double-positive, 11,615 single-positive, and 226,337 seronegative individuals were identified. Overall IRs of RA were 5.98, 2.96, and 0.18 in the double-positive, single-positive, and seronegative group, respectively. The cumulative incidence of RA at 5 years since start of follow-up was 3.0%, 1.4%, and 0.1% in the double-positive, single-positive, and seronegative groups, respectively (Figure 1). The overall HR for developing RA was 38.9 (95% CI 31.6 to 47.9) in the double-positive group and 18.1 (95% CI 14.6 to 22.5) in the single-positive group compared to seronegative. The highest HRs in double-positive and single-positive groups were observed within one year after test: HR 49.1 (95% CI 38.7 to 62.1), and 21.6 (95%CI 16.9 to 27.7). The HR was still significantly increased after five years in the double-positive group, but not in the single-positive group: HR 14.2 (95% CI 4.2 to 40.5), and 3.4 (95% CI 0.7 to 15.4) (Table 1). Conclusion: In individuals tested for RA-related autoantibodies, the risk of developing RA was multifold increased in double-positive and single-positive compared with seronegative individuals. The risk was most pronounced for the double-positive group and within the first year after testing. Single-positive individuals were at increased risk of RA for up to five years after testing, indicating that monitoring in this period might be beneficial. In double-positive individuals, the risk remained increased, and monitoring might still be necessary beyond five years after test. The majority of individuals in both seropositive groups did not develop RA over time. This indicates that many other factors than autoantibodies should be considered when monitoring and evaluating the risk of RA in seropositive individuals. REFERENCES: 1 Van Zanten A, Arends S, Roozendaal C, Limburg PC, Maas F, Trouw LA, m.fl. Presence of anticitrullinated protein antibodies in a large population-based cohort from the Netherlands. Ann Rheum Dis. juli 2017;76(7):1184–90. 2 Jónsson T, Thorsteinsson J, Kolbeinsson A, Jónasdóttir E, Sigfússon N, Valdimarsson H. Population study of the importance of rheumatoid factor isotypes in adults. Ann Rheum Dis. 1. juli 1992;51(7):863–8. 3 Nielsen SF, Bojesen SE, Schnohr P, Nordestgaard BG. Elevated rheumatoid factor and long term risk of rheumatoid arthritis: a prospective cohort study. BMJ. 6. september 2012;345:e5244. Acknowledgements: The study has been supported by the Danish Rheumatism Association. Disclosure of Interests: Ida Vestergaard Vittrup: None declared, Constance Jensina de Saint-Aubain: None declared, Rasmus Westermann: None declared, Kirsten S. Duch: None declared, Salome Kristensen: None declared, Lene Dreyer Lene Dreyer has received research grant (paid to her institution) from BMS and Abbvie outside the current manuscript. She is member of the steering committee of the Danish Rheumatology Quality Registry (DANBIO, DRQ), which receives public funding from the hospital owners and funding from pharmaceutical companies.