EFFICACY AND SAFETY OF RITUXIMAB (RTX) IN REFRACTORY LUPUS NEPHRITIS (LN) FROM REAL-WORLD LOOPS REGISTRY

O039 / #695 Topic: AS15 - Lupus Nephritis-Clinical ABSTRACT CONCURRENT SESSION 06: LUPUS NEPHRITIS – CLINICAL OUTCOMES, PREDICTION AND THERAPY 23-05-2025 1:40 PM - 2:40 PM Background/Purpose In 2023, Rituximab (RTX) therapy for lupus nephritis was approved in Japan. However, the efficacy and safety in real-world clinical practice have not been validated. This study aimed to assess the efficacy and safety of RTX for LN in real-world clinical practice. Methods Patients with LN who received remission induction therapy with high- or moderate-dose GC or GC pulse, combined with HCQ+RTX (RTX group, n=33), +MMF (MMF group, n=77), or +CYC group (CYC group, n=24) after May 2016 (when MMF was approved in Japan) were included. The efficacy and safety were compared among groups. The primary endpoint was the achievement rate of complete renal response (CRR) and uPCR <1.0 at week 52. The secondary endpoints were retention rate, adverse events, and GC-sparing effect. In addition, peripheral blood immunophenotyping was performed on age- and gender-matched HCs and patients with LN. In patients with LN, immune phenotyping was also conducted before and after treatment. Results Treatment retention was 90.9% (30/33) in the RTX group, 90.9% (70/77) in the MMF group, and 70.8% (17/24) in the CYC group. The most common adverse events were infusion reactions (27.3%) in RTX and infections in MMF (32.4%) and CYC (58.3%). SLEDAI and BILAG scores significantly decreased in all groups. CRR achievement rates were 39.4% (RTX), 48.1% (MMF), and 37.5% (CYC), and uPCR <1.0 rates were 82.7% (RTX), 87.0% (MMF), and 81.3% (CYC), with no significant differences among the groups. GC-sparing effects were also similar across the groups (RTX: -87.8%, MMF: -84.4%, CYC: -86.7%). Immunophenotyping revealed that class-switched memory B cells (CM B cells) and plasmocytes were elevated in SLE patients compared to healthy controls (HCs). In the RTX group, naïve B cells, CM B cells, and plasmocytes were found to have disappeared at 26 weeks. In cases achieving CRR in the RTX group, CM B cells and plasmocytes remained undetectable at 52 weeks, whereas in non-CRR cases, they showed a re-increase. Changes in T cells were not associated with treatment efficacy in the RTX group. In the MMF and IVCY groups, naïve B cells, CM B cells, and plasmocytes were significantly decreased at week 52; however, this decrease was not associated with treatment efficacy. On the other hand, in cases achieving CRR in the MMF and IVCY groups, activated CD4 + T cells and activated Th1 cells were significantly reduced. Conclusions Immunosuppressive drugs and RTX had different effects on the immune phenotype. RTX can be an effective treatment option for LN in real-world clinical practice.