Abstract
OBJECTIVES: Neuropsychiatric SLE (NPSLE) lacks evidence-based treatment strategies. This study compared the effectiveness and safety profiles of obinutuzumab (OBZ) and rituximab (RTX) in patients with NPSLE. METHODS: Patients with new-onset NPSLE meeting British Isles Lupus Assessment Group grade A criteria who received either OBZ or RTX between 2018 and 2024 at Renji Hospital, Shanghai Jiao Tong University School of Medicine (with ≥12 months follow-up) were included. Propensity score matching (1:2 ratio) based on age, sex and SLE Disease Activity Index (SLEDAI) was performed. The primary outcome was complete or partial response at 12 months. Kaplan-Meier curves compared therapeutic effectiveness. Safety profiles of OBZ and RTX were recorded. RESULTS: 27 patients with new-onset NPSLE were included in this retrospective study, with 9 patients receiving OBZ and 18 patients receiving RTX. At 12 months, the primary outcome was achieved in 8 of 9 patients in the OBZ group and 13 of 18 patients in the RTX group (88.9% vs 72.2%; OR: 3.08, 95% CI 0.30 to 31.33; p=0.34). Compared with the RTX group, the OBZ group demonstrated higher lupus low disease activity state attainment (74.1% vs 52.3%; p=0.049), lower SLEDAI-2000 Scores (median (IQR): 2 (1-2) vs 4 (2-4.25); p=0.04) and a trend towards higher B cell depletion rates at 12 months (57.1% vs 20.0%; p=0.08). OBZ treatment significantly shortened hospitalisation by 7 days (14.7±5.4 vs 21.9±11.9 days; p=0.04) and achieved a deeper B cell depletion at 6 months (median CD19+B cells: 0.4 (0-1.4) vs 3.5 (2-19.3) cells/µL; p=0.01), compared with the RTX group. Safety profiles were comparable between groups, with both treatments well tolerated. No deaths occurred. CONCLUSION: These findings suggest OBZ may induce superior clinical responses in NPSLE through enhanced B cell depletion, with acceptable safety at 12 months, calling for further exploration.