ABS1004 UNRAVELING THE INFLUENCE OF RHEUMATOID FACTOR ON RA TREATMENT SUCCESS

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Background: Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by synovial inflammation and articular bone destruction. A hallmark of RA is the presence of autoantibodies, such as rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). RF are autoantibodies that target the Fc portion of other immunoglobulins (IGs). Previous studies have shown that responses to targeted therapies with varying structures may differ depending on the patient's baseline RF levels. High RF levels, defined as ≥203 UI/mL prior to initiating b/tsDMARD have been previously associated with a shorter drug persistence and poorer clinical response in patients receiving monoclonal antibody (mAb) TNF inhibitors (TNFi). It has been hypothesized to occur due to RF binding to the Fc region of mAb TNFi, leading to enhanced drug clearance, and reduced clinical efficacy. Interestingly, this has not been observed with pegylated Fab fragment TNFi (Certolizumab, CZP), possibly due to the absence of an Fc fragment. However, it remains unknown whether basal RF levels could similarly influence the therapy response in RA patients treated with non-TNFi bDMARD or JAK inhibitors (JAKi), which have distinct structural properties. Objectives: To investigate whether the presence of RF at titres ≥203 IU/ml is associated with the clinical response of b/tsDMARDs with a mechanism of action different from TNFi. Methods: A retrospective longitudinal study was conducted, including patients with RA from our hospital who had been treated with Certolizumab (CZP), Rituximab (RTX), Tocilizumab (TCZ) or JAKi at most, as third-line treatment. Sociodemographic data, use of conventional synthetic DMARDs (csDMARDs), bDMARDs, corticosteroids, RF levels prior to start of b/tsDMARD treatment were collected. Analytical and clinical parameters of inflammatory activity at prior and after 6 months of starting b/tsDMARD were collected. For descriptive statistical analysis, patients were divided into four groups according to the b/tsDMARD received, and group comparisons were performed using the Chi-square test or Fisher's exact test for categorical variables, and the ANOVA or Kruskal-Wallis test for continuous comparative variables. For comparisons of clinical response, patients were compared according to RF status [low levels (LL): <203 IU/mL and high levels (HL): ≥203 IU/mL] in each therapy group using U Mann Whitney test. Results: A total of 219 patients with RA were included, of which 43 (20%) received CZP, 46 (21%) RTX, 97 (44%) TCZ, and 33 (15%) JAKi. Sociodemographic, serological and clinical parameters before starting the b/tsDMARD are summarized in Table 1. Patients treated with CZP were younger in comparison of the remaining therapy groups (46.6y in CZP vs 63.5y in RTX vs 57.5y in TCZ vs 58.7y in JAKi, p<0.05). No differences in clinical activity by DAS28 and SDAI at baseline among the different drugs. In addition, naïve patients to b/tsDMARDs were more frequent in CZP group (81% in CZP vs. 19.6% in RTX vs. 45% in TCZ vs.24% in JAKi, p<0.001). In TCZ group, patients with basal high levels of RF showed a higher 6 month-DAS28 than those patients with low levels (3.6±1.1 in HL vs 2.7±1.26 in LL, p=0.03). No statistically significant differences in clinical activity measured by DAS28 were observed in the rest of therapy groups (see Figure 1A). In addition, when clinical activity was assessed using 6 month-SDAI, a poorer response was again observed in patients treated with TCZ with high baseline RF levels (14.3±9.3 in HL vs 8.0±6.5 in LL, p=0.049) without differences in the other drugs (see Figure 1B). Conclusion: High baseline RF levels (≥203 IU/mL) were associated with a 6-month poorer clinical response to TCZ, as evidenced by higher DAS28 and SDAI. This effect was not observed with CZP, RTX, or JAKi, suggesting that the influence of RF on therapeutic response may vary depending on the structural properties of the drug. These findings highlight the need to consider RF levels when tailoring treatment strategies for RA patients. Table 1. Baseline stratified characteristics. Figure 16-month clinical activity measured by DAS28 (A) and SDAI (B) according to basal RF levels in the different therapy groups. REFERENCES: NIL . Acknowledgements: This work was conducted in the context of an unrestricted grant from UCB. Disclosure of Interests: None declared . © The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.

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