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<h2>Abstract</h2><h3>Background:</h3> Ozoralizumab (OZR) is a next-generation anti-tumor necrosis factor (TNF) antibody which is a trivalent NANOBODY®* compound [1]. The Phase II/III OHZORA trial evaluated the efficacy and safety of OZR at 30 or 80 mg for 52 weeks in patients with active rheumatoid arthritis (RA) despite methotrexate therapy [2, 3]. Generally, the efficacy of anti-TNF antibodies containing the fragment crystallizable (Fc) portion is reduced in patients with high titres of rheumatoid factor (RF) [4, 5]; on the other hand, certolizumab pegol (CZP) that lacks the Fc portion is effective regardless of RF titres [6, 7]. This may be attributed to the immune complex formed by RF pentamer and anti-TNF antibody with the Fc portion that is phagocytosed via Fc receptors expressed on macrophages in patients with high RF titres, which may reduce the blood concentration of the anti-TNF antibody [8, 9]. However, the efficacy of OZR, which lacks the Fc portion in patients with high RF titres, remains unclear. *NANOBODY® is a registered trademark of Ablynx NV, an affiliate of Sanofi. Ablynx NV originally discovered and performed initial development of the NANOBODY ® compound ozoralizumab. <h3>Objectives:</h3> The primary objective of the current study was to evaluate the efficacy of OZR in patients with RA and varying RF and anti-citrullinated peptide antibody (ACPA) titres. The secondary objective was to evaluate the changes in RF and ACPA titres following OZR treatment. <h3>Methods:</h3> A post hoc analysis was conducted on data from the OHZORA trial, which included 381 Japanese patients with RA who were treated with either 30 or 80 mg OZR. Patients were classified into four groups based on the baseline RF or ACPA titre quartiles. The disease activity scores, RF and ACPA titres, plasma OZR concentrations, and OZR-neutralizing antibody levels were evaluated. Statistical analyses included the Kruskal–Wallis test, two-way ANOVA, and correlation analysis. <h3>Results:</h3> Treatment with OZR 30 mg significantly reduced disease activity in all the groups (P <0.001, Figure 1A), and the reduction in disease activity scores was comparable among the groups. Treatment with OZR 30 mg decreased the mean RF and ACPA titres from 149.5 to 71.1 IU/mL (P <0.001, Figure 1B) and 299.6 to 237.6 U/mL (P <0.001, Figure 1C), respectively. Effective trough concentrations of OZR were maintained for up to 52 weeks in all the groups (Figure 1D), and baseline RF and ACPA titres were not associated with the generation of OZR-neutralizing antibodies. <h3>Conclusion:</h3> OZR is an effective anti-TNF treatment for RA, regardless of RF and ACPA titres, and exhibits promise as a novel therapeutic option. <h3>REFERENCES:</h3> [1] Takeuchi T. Mod Rheumatol. 2023;33(6):1059-67. [2] akeuchi T. Arthritis Rheumatol. 2022;74(11):1776-85. [3] Tanaka Y. Mod Rheumatol. 2023;33(5):883-90. [4] Bobbio-Pallavicini F. Ann Rheum Dis. 2007;66(3):302-7. [5] Potter C. Ann Rheum Dis. 2009;68(1):69-74. [6] Nakayama Y. Rheumatol Int. 2022;42(7):1227-34. [7] Tanaka Y. Int J Rheum Dis. 2023;26(7):1248-59. [8] Junker F. Front Immunol. 2020;11:1393. [9] Martinez-Feito As. Clin Exp Rheumatol. 2024;42(5):999-1005. Figure 1Summary of this study. A total of 143 patients who received ozoralizumab (OZR) 30 mg over 52 weeks were classified into four groups based on the baseline rheumatoid factor (RF) titre quartiles (RF1: RF 3–20 IU/mL, RF2: 20–49 IU/mL, RF3: 49–153 IU/mL, RF4: 153–2029 IU/mL). (A) changes in DAS28-CRP were shown. The last observation carried forward method was used. (B) the mean change of the RF titre, (C) the mean change of anti-CCP antibody titre, and (D) plasma OZR concentrations were shown. Data are shown as mean±SD. *** <i>P</i><0.001. <h3>Acknowledgements:</h3> <b>NIL</b>. <h3>Disclosure of Interests:</h3> Ryu Watanabe AbbVie, Asahi Kasei, Chugai, Eli Lilly, GSK, and UCB Japan, AbbVie, Yoshiya Tanaka Abbvie, Eisai, Chugai, Eli-Lilly, Behringer-Ingelheim, GlaxoSmithKline, Taisho, AstraZeneca, Daiichi-Sankyo, Gilead, Pfizer, UCB, Asahi-kasei, Astellas, Behringer-Ingelheim, Taisho, Chugai, Tsutomu Takeuchi AbbVie GK, Chugai, Eli Lilly Japan, Eisai, Gilead Sciences Inc, Pfizer Japan Inc, Taisho Pharma., AbbVie GK, Eli Lilly Japan, Gilead Sciences, Inc., Mitsubishi-Tanabe, Taisho Pharma, SHUNSUKE OKAMOTO Taisho Pharmaceutical Co. Ltd., Masanao Kyuuma Taisho Pharmaceutical Co. Ltd., Rumiko Matsumoto Taisho Pharmaceutical Co. Ltd., Yoichi Nakayama Asahi Kasei Pharma Corp., Chugai Pharmaceutical Co., and AbbVie Inc., Masao Katsushima: None declared, Motomu Hashimoto Brystol Meyers, Chugai, Eisai, Eli Lilly, Tanabe Mitsubishi, Abbvie, Asahi Kasei, Astellas, Brystol Meyers, Eisai, Daiichi Sankyo, Eli Lilly, Novartis Pharma, Taisho Toyama. © 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.