Abstract

Background:Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by cartilage and bone destruction, which can lead to joint dysfunction and disability. Antibodies’ role as biomarkers in RA has been recently increasing: Anti-citrullinated protein antibodies (ACPAs) are the most specific one (60–70% of cases); whereas rheumatoid factor (RF) is seen in nearly 70% of cases, however, it is less specific than ACPA for RA diagnosisi. ACPA/RF positivity is related to a more severe phenotype and a rapid progression to clinically apparent RAii. Other biomarkers are Antinuclear Antibodies (ANAs), which have been related to a worse response to bDMARD treatmentiii.iNishimura K, Sugiyama D, Kogata Y, Tsuji G, Nakazawa T, Kawano S, et al. Meta-analysis: Diagnostic accuracy of anti-cyclic citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis. Vol. 146, Annals of Internal Medicine. American College of Physicians; 2007. p. 797–808.iiLingampalli N, Sokolove J, Lahey LJ, et al. Combination of anti-citrullinated protein antibodies and rheumatoid factor is associated with increased systemic inflammatory mediators and more rapid progression from preclinical to clinical rheumatoid arthritis. Clin Immunol. 2018;195:119-126.iiiIshikawa Y, Hashimoto M, Ito H, Tanaka M, Yukawa N, Fujii T, et al. Anti-nuclear antibody development is associated with poor treatment response to biological disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis. Semin Arthritis Rheum. 2019;49(2):204–10.Objectives:Our aim was to compare in terms of mean differences the disease activity according to the presence of RF, ACPA, and ANA in an outpatient clinic-based cohort of Colombian RA patients.Methods:We conducted a retrospective cohort study with clinical-epidemiological data obtained from May 2013 to Feb. 2020 of patients with RA diagnosis based on the 2010 ACR/EULAR classification criteria. The patients were stratified into eight subgroups according to their autoantibody status. Disease activity, assessed by the DAS28-ESR, was recorded at baseline and after 3, ≈ 12, ≈ 24, and ≈ 36 (+/- 3) months. Mean DAS28-ESR differences were calculated by applying the Wilcoxon non-parametric rank test for two independent samples.Results:Data of 384 patients who all completed 36 months of follow-up, from an ongoing cohort of ≈1100 patients, were included in the analysis. On our primarily female (n=294, 76,8%) population, RF+ / ACPA+ / ANA+ subgroup was the most prevalent (n=183; 47,8%); interestingly, it was the one with the highest disease activity at baseline. After three months, all showed disease activity reduction; however, when completing follow-up, triple-positive, triple-negative and ANA-positive patients did not reach remission. Statistically significant mean differences were displayed when comparing overall and baseline mean DAS28-ESR scores for ANA+ vs ANA- patients, as shown in table 1.Table 1.Disease activity mean differences when comparing ANA+ vs ANA- patientsBaselineANA+(n = 218)ANA-(n = 165)Mean differencep value4,053,620,430,01433,323,140,180,396123,132,890,240,059242,802,680,110,563362,802,580,220,098Overall3,222,980,240,002Conclusion:In our study population, triple-positive and ACPA+/ANA+ patients showed higher disease activity at baseline and on average during the follow-up period; furthermore, ANA positivity was shown to be conditional on a significant difference for higher disease activity. RF and ACPA positive have long since been described as determinants for disease activity; nonetheless, our research provides insights for the consideration of ANA titers as a novel addition that enables the preamble of triple-positivity as something to be acknowledged. Caution must be applied when interpreting these results, understanding the need for this matter to be subject of future research with greater sample size, and taking into account other potentially confounder variables.Figure 1.Mean disease activity for each stratumDisclosure of Interests:None declared

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