AB0730 ANALYSIS OF CHANGES IN ANTIGEN-SPECIFIC ACPA TITERS AND TREATMENT RESPONSE IN A MULTICENTER PROSPECTIVE OBSERVATIONAL STUDY OF JAPANESE NEWLY ABATACEPT (ABT) ADMINISTERED RA PATIENTS (ORIJIN STUDY)
Authors: M. Kusaoi, G. Murayama, T. Azuma, S. Hirata, N. Takahashi, A. Mitsuo, Y. Abe, K. Minowa, T. Kawamoto, A. Katagiri, M. Matsushita, K. Tada, M. Ogasawara, H. Amano, S. Morimoto, K. Yamaji, N. Tamura
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> The importance of the role of ACPA in the pathogenesis of rheumatoid arthritis has been reported. ABT is a biologic DMARD that inhibits T-cell activation, and its efficacy is higher in ACPA-positive patients. However, it remains unclear which patients with positive autoantibodies to specific citrullinated proteins are particularly likely to benefit from ABT. <h3>Objectives:</h3> We designed a prospective 2-year observational follow-up study (ORIJIN study) of bDMARDs-naïve Japanese rheumatoid arthritis patients newly started subcutaneous ABT injections. This study was planned to analyze the association between clinical information and antigen-specific ACPA expression profiles in patients who responded to ABT. <h3>Methods:</h3> Patients with active rheumatoid arthritis inadequately respond to at least one csDMARD and decided to start subcutaneous ABA as a first bDMARD were eligible for observation. A total of 92 patients from six hospitals were enrolled in this observational study in the period of December 2016 to November 2020. The Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), Disease Activity Score with 28-joint count C-reactive protein (DAS28-CRP), and DAS28 erythrocyte sedimentation rate (DAS28-ESR). Responders were defined as achieving low disease activity or remission measured by SDAI at 12 or 24 months Human leukocyte antigen (HLA) genotype was examined with written informed consent. Antigen-specific ACPA was investigated for 13 citrullinated peptides (Apolipoprotein E, Biglycan, 2 kinds of Clusterin, Enolase, 4 kinds of Fibrinogen A, Filaggrin, 2 kinds of Histone(H2A/a 1-20, H2B/a 62-81), and Vimentin) using a custom multiplex bead array (MagPlex<sup>TM</sup>). The fluorescence intensity was measured using the Luminex® System. <h3>Results:</h3> The SDAI remission rates after ABT in 92 patients were 22.8% and 29.3% at 12 and 24 months, respectively, and the rates of achieving low disease activity (SDAI≦11) were 64.1% and 74.7% at 12 and 24 months, respectively. The continuation rates of ABT at 12 and 24 months were 84.8% and 65.2%, respectively. Antibody titers against citrullinated fibrinogen (FibrinogenA_211_230) at 12 and 24 months in the group achieving low disease activity or below (364.7±585.2, 249.6±308.1) compared with the non-remission group (961.1±1330.7, 1074±1423.1), It was significantly lower than before treatment (p&lt;0.05, Wilcoxon signed rank test). <h3>Conclusion:</h3> The antibody titer against citrullinated fibrinogen may be related to the therapeutic effect of ABT. Further investigation is required in the future. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Makio Kusaoi Asahi Kasei Medical Co.,Ltd, Asahi Kasei pharma Co.,Ltd, Bristol-Myers Squibb(BMS), Chugai Pharmaceutical Co.,Ltd, Goh Murayama: None declared, Takanori Azuma: None declared, Shintaro Hirata AbbVie/Abbott, Asahi-Kasei Pharma, Astellas, Ayumi, Bristol-Myers Squibb(BMS), Chugai Pharmaceutical Co.,Ltd, Eisai Co.,Ltd, Eli Lilly, Gilead, GlaxoSmithKlein(GSK), janssen, kyorin, Novartis, Pfizer, Sanofi, Tanabe-Misubishi, UCB, AbbVie/Abbott, Asahi-Kasei Pharma, Ayumi, Chugai Pharmaceutical Co.,Ltd, Eisai Co.,Ltd, Eli Lilly, Otsuka, Pfizer, Sanofi, Shionogi, Tanabe-Misubishi, UCB, Nobunori Takahashi AbbVie/Abbott, Astellas Pharma Inc, Bristol-Myers Squibb(BMS), Chugai Pharmaceutical Co.,Ltd, Eisai Co.,Ltd, Eli Lilly, janssen Pharmaceutical KK., Pfizer Japan, Tanabe-Misubishi, UCB, Akiko Mitsuo: None declared, Yoshiyuki Abe: None declared, Kentaro Minowa: None declared, Toshio Kawamoto: None declared, Akira Katagiri: None declared, Masakazu Matsushita: None declared, Kurisu Tada: None declared, Michihiro Ogasawara: None declared, Hirofumi Amano: None declared, Shinji Morimoto: None declared, Ken Yamaji Asahi Kasei Medical Co.,Ltd, Asahi Kasei pharma Co.,Ltd, Bristol-Myers Squibb(BMS), Chugai Pharmaceutical Co.,Ltd, Naoto Tamura AbbVie/Abbott, Bristol-Myers Squibb(BMS), Chugai Pharmaceutical Co.,Ltd, Eisai Co.,Ltd, Eli Lilly, GlaxoSmithKlein(GSK), janssen, Mitsubisi Tanabe Pharma Corporation, Novartis.