ABS0793 EFFECTIVENESS OF CYTOTOXIC T-LYMPHOCYTE ANTIGEN-4-Ig AND JANUS KINASE INHIBITOR IN RHEUMATOID ARTHRITIS PATIENTS WITH HIGH RHEUMATOID FACTOR LEVELS: A RETROSPECTIVE COMPARATIVE STUDY IN SINGLE CENTER

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Background: High levels of Rheumatoid Factor (RF) are recognized as a prognostic factor for poor joint outcomes. Therefore, treatment selection for rheumatoid arthritis (RA) patients with high RF levels is critically important. In RA patients with high RF levels, there have been previous reports of the usefulness of Cytotoxic T-Lymphocyte Antigen-4-Ig (CTLA-4-Ig) [1], additionally the therapeutic efficacy of tumor necrosis factor inhibitors (TNFi) without fragment crystallizable（Fc） portion has been reported to be superior to that of TNFi with FC portion [2]. This suggests that different treatment drugs may have varying effects. However, there is a lack of studies directly comparing Janus kinase inhibitors (JAKi) and other biological disease-modifying antirheumatic drugs (bDMARDs) in patients with high RF levels. Objectives: The aim of our study is to explore the optimal treatment for RA patients with high RF levels. Methods: We conducted two analyses to examine the relationship between high RF levels and drug efficacy: (1) an evaluation of the retention rates of bDMARDs and JAKi in patients with high RF levels, and (2) a comparison of drug-specific retention rates between high RF and low RF groups. We retrospectively extracted data on RA patients who initiated bDMARDs or JAKi and received treatment at our institution between 2013 and 2023. Based on a previously reported cutoff value (165 IU/mL) [3], patients were divided into two groups: high RF (≧165 IU/mL) and low RF (<165 IU/mL). The 6-month drug retention rates of bDMARDs (TNFi, CTLA-4-Ig, and anti-interleukin-6 receptor [aIL-6R]) and JAKi were compared in the high RF group. Additionally, the retention rates of the four drugs were compared between the high RF and low RF groups. Survival analysis was performed using the Log-rank test, and multivariate analysis was conducted using the Cox proportional hazards model. A P -value <0.05 was considered statistically significant. Results: We included 1,896 RA patients treated at our institution. Among them, 732 patients who initiated bDMARDs or JAKi were identified. After excluding cases without RF measurements at treatment initiation, 757 treatment courses (TCs) were analyzed, comprising 242 TCs in the high RF group and 515 TCs in the low RF group. The breakdown of drug usage among the 757 TCs was as follows: 115 TCs (15.2%) with CTLA-4-Ig, 176 TCs (23.2%) with aIL-6R, 164 TCs (21.7%) with JAKi, and 302 TCs (39.9%) with TNFi. Among the TNFi group, 31 TCs involved Fc-free agents (certolizumab pegol and Ozoralizumab). Baseline characteristics revealed that the high RF group had a significantly higher median age at treatment initiation, with an interquartile range (IQR) of 66.4 years (53.8–74.1) compared to 62.9 years (49.1–72.8) in the low RF group (p = 0.03). Additionally, the high RF group exhibited higher disease activity, with a median CDAI of 11.35 (IQR 6.57–16.08) compared to 7.20 (IQR 2.70–13.50) in the low RF group (p < 0.001). In the high RF group, a comparison of the 6-month drug retention rates among the four drugs revealed that CTLA-4-Ig had the highest retention rate; however, the difference did not reach statistical significance (p = 0.066, Figure 1). In contrast, a multivariable analysis using a Cox proportional hazards model, adjusted for potential confounders including baseline age, sex, disease duration, anti-citrullinated protein antibody （ACPA） titer, CDAI at drug initiation, and concomitant use of glucocorticoids and MTX, showed significant differences in retention rates for TNFi and IL-6R. CTLA-4-Ig showed superior retention compared to TNFi and aIL-6R: TNFi (HR: 3.65, 95% CI: 1.62 to 8.17, P value=0.0016) and aIL-6R (HR: 2.40, 95% CI: 1.14 to 5.82, P value=0.002). On the other hand, no statistically significant difference was found for JAKi (HR: 1.92, 95% CI: 0.96 to 8.17, P value=0.062). Furthermore, a comparison of drug retention rates between the high RF group and the low RF group showed that aIL-6R and TNFi had significantly lower retention rates in the high RF group compared to the low RF group. In contrast, the retention rates for CTLA-4-Ig and JAKi were similar between the two groups (Figure 2). These findings were consistent with the results of the Cox proportional hazards model, which showed no statistically significant differences for CTLA-4-Ig (HR: 0.92, 95% CI: 0.43–1.97, p=0.83) and JAKi (HR: 0.72, 95% CI: 0.43–1.22, p=0.22). Conclusion: In high RF levels group, CTL-4-Ig was highest retention rate, while TNFi and aIL-6R showed lower retention rates. JAKi retention was comparable to CTLA-4-Ig and was less influenced by RF levels, supporting its use as a second-line option for high RF patients. Based on our results of the survival analysis, it will be necessary to consider comparing disease activity to further investigate the effectiveness of treatments based on RF levels. REFERENCES: [1] Hiroki Kobayashi et al, Rheumatology (Oxford). 2024 Nov 5: keae598. [2] Josef S Smolen et al, Rheumatology (Oxford). 2024 Nov 1;63(11):3015-3024. [3] Yoichi Nakayama et al, Rheumatology International. 2022 Jul;42(7):1227-1234. Acknowledgements: NIL . 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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