Abstract

Background: Lupus nephritis (LN) is one of the most critical organ involvement in systemic lupus erythematosus (SLE). While there are effective treatment options such as MMF and cyclophosphamide, there are still unmet medical needs: refractory cases to existing therapies and difficult cases to reduce GC. Therefore, the emergence of new treatment options is expected. Recently, rituximab (RTX), an anti-CD20 antibody, is expected to be a new treatment option for LN based on the results of clinical trials. Indeed, the EULAR recommends the use of RTX for refractory LN. In Japan, RTX for LN was approved in August 2023, ahead of the world. However, the effectiveness and safety of RTX in real-world clinical practice have not been fully verified. Objectives: This study aimed to assess the effectiveness and safety of RTX for LN in real-world clinical practice. Methods: This study included 117 patients with LN. The effectiveness and safety were compared between High-dose GC + RTX group (RTX group, n = 58) and high-dose GC + CY and MMF group (standard of care: SoC group, n = 59) in remission induction therapy for patients with LN. Both groups were treated in addition to standard of care including HCQ. Selection bias was minimized by the propensity score-based inverse probability of treatment weighting (PS-IPTW) method and compared between the groups. The primary endpoint was the Complete Renal Response (CRR) achieving rate and uPCR less than 1.0 (g/g・cre) at week 52. Secondary endpoints were treatment retention rate, safety, SLEDAI, and GC reduction rate at 52 weeks. Peripheral blood immunophenotypes (CD4 T cell, CD8 T cell, B cell, NK, monocyte, DC) of LN(n=76) just before the remission induction therapy were compared to those of age- and sex-matched HC (n=109). Additionally, the impact of RTX on immunophenotypes was evaluated by comparing before and after RTX in 21 patients. Results: The 52-week treatment retention rate was 94.8% (55/58) in the RTX group and 83.1% (49/59) in the SoC group, with no difference between the two groups. Infusion reactions were the most frequent adverse event in the RTX group at 20.7% (12/58), and infections were the most frequent in the SoC group at 47.5% (28/59). SLEDAI scores significantly decreased in both groups. Patient baseline characteristics were adjusted by PS-IPTW method. The primary endpoint achievement rate was 1) CRR achieving rate: RTX group; 58.1%, SoC group; 52.2% (p=0.38), uPCR<1.0 achieving rate: RTX group; 83.2%, SoC; 81.3% (p=0.54). There was no significant difference between the groups. There was also no difference in GC sparing effect, the secondary endpoint, between the two groups (RTX group; -81.1%, SoC group; -89.3%, p=0.65). Immune phenotyping revealed increased class-switched memory B cells (CM B cells: CD19+ CD27+ IgM-) and plasmocytes (CD19+ CD27+ CD38+) in SLE compared to HCs. Naïve B cells (CD19+ CD27- IgM+), CM B cells, and plasmocytes disappeared after 26 weeks of RTX introduction. plasmocytes remained low for 52 weeks in cases that achieved the primary endpoint(n=16). On the contrary, CM B cells and plasmocytes increased in cases that did not achieve the primary endpoint (n=5). Patients who relapsed within 3 years after achieving the primary endpoint by RTX were 5/16 cases, in which CM B cells and plasmocytes increased again. Naïve B cells re-elevated while CM B cells and plasmocytes remained absent in the non-relapse cases. Conclusion: Rituximab can be an effective treatment option in real-world clinical practice achieving remission and suppressing relapse by depleting CM B cells and plasmocytes. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: Masanobu Ueno Masanobu Ueno has received a speaking fee from GlaxoSmithKline., Shingo Nakayamada S. Nakayamada has received consulting fees, speaking fees, and/or honoraria from Bristol-Myers, AstraZeneca, Pfizer, GlaxoSmithKline, Astellas, Asahi-kasei, Sanofi, Abbvie, Eisai, Chugai, Gilead, and Boehringer Ingelheim, and has received research grants from Mitsubishi-Tanabe., S. Nakayamada has received consulting fees, speaking fees, and/or honoraria from Bristol-Myers, AstraZeneca, Pfizer, GlaxoSmithKline, Astellas, Asahi-kasei, Sanofi, Abbvie, Eisai, Chugai, Gilead, and Boehringer Ingelheim, and has received research grants from Mitsubishi-Tanabe., Ippei Miyagawa: None declared, Satoshi Kubo Satoshi Kubo has received speaking fees from Eli Lilly, GlaxoSmithKline, Bristol-Myers, Abbvie, Eisai, Pfizer, Astra-Zeneca and also research grants from Daiichi-Sankyo, Abbvie, Boehringer Ingelheim, and Astellas., Yusuke Miyazaki Y. Miyazaki has received speaking fees from Eli Lilly, and has received research grants from GlaxoSmithKline., Kentaro Hanami: None declared, Koshiro Sonomoto: None declared, Hiroaki Tanaka: None declared, Yoshiya Tanaka Yoshiya Tanaka has received speaking fee from Eli Lilly, AstraZeneca, Abbvie, Gilead, Chugai, Behringer-Ingelheim, GlaxoSmithKline, Eisai, Taisho, Bristol-Myers, Pfizer, and Taiho., Yoshiya Tanaka has received grant from Mitsubishi-Tanabe, Eisai, Chugai, and Taisho.