Background/Purpose: Rituximab (RTX) has been commonly used for the treatment of patients with severe or refractory systemic lupus erythematosus (SLE), yet real-worlddata concerningRTX as the first-linetreatment in newly diagnosedmoderate-to-severe SLE patients is lacking. Methods: We conducted a retrospective cohort study using a newly diagnosed (< 3 months) hospitalized Systemic Lupus Inception Cohort (hSLIC) at our center between 1 April 2013 and 1 September 2022. All patients were followed up for at least 12 months or until death. The cohort included patients on RTX (n=104) as the first-line treatment and those on conventional immunosuppressants (IS) (n=154) as comparators. Propensity score-based inverse probability of treatment weighting (IPTW) was used to minimize possible confounding factors. Primary outcome analyses included attainment of modified lupus low disease activity state (mLLDAS) and remission, by 12 months. Secondary outcomes focused on mortality, major flare rates, and the incidence of adverse events of interest, i.e., major infections. Results: After IPTW, 76.0%/50.5% of RTX-treated patients achieved mLLDAS/remission versus 45.8%/9.7% in the conventional IS group during 12 months follow-up, respectively (p=0.005 and p< 0.001). Sensitivity analyses with renal or neuropsychiatric lupus removal and timeline breakout (pre versus post November 2019) confirmed the robustness of RTX’s efficacy in achieving mLLDAS and remission outcomes. Additionally, the incidence of major infections was similar between the two groups (12.5% vs. 8.4%, p=0.288). Conclusion: In patients with newly diagnosed moderate-to-severe SLE, upfront treatment with RTX was associated with improved clinical outcomes compared to conventional immunosuppressive therapy, in terms of achieving low disease activity or remission by 12 months.
