To evaluate and compare the clinical efficacy and safety of belimumab and telitacicept, each combined with standard therapy, in the treatment of LN, and to identify the subgroups most likely to benefit from different B-cell-targeted strategies through stratified analyses based on baseline urine protein-to-creatinine ratio (uPCR).

This multicenter retrospective study included 212 patients with LN who were treated at the Second Affiliated Hospital of Guangzhou Medical University and Sun Yat-sen Memorial Hospital, Sun Yat-sen University, between January 2018 and November 2025. According to treatment regimen, patients were divided into the MMF group (n=78), low-dose CTX group (n=25), belimumab combination group (n=49), and telitacicept combination group (n=60). The primary endpoint was CRR at 6 months. Secondary endpoints included partial renal response (PRR), overall renal response (ORR), changes in the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), glucocorticoid tapering, and changes in immunologic indicators.Multivariable Logistic regression models were constructed, with subgroup and interaction analyses performed according to baseline uPCR and pathological scores, including activity index (AI) and chronicity index (CI).

At 6 months, the CRR rate differed significantly among the four groups (71.7% in the telitacicept combination group vs 63.3% in the belimumab combination group vs 51.3% in the MMF group vs 44.0% in the CTX group, P=0.035). For secondary endpoints, significant differences were observed among the four groups in SLEDAI-2K reduction and the proportion achieving glucocorticoid tapering targets (both P<0.05). In addition, the B-cell-targeted groups showed better regulation of immunoglobulins than the conventional-treatment groups, especially for IgA. In the direct comparison between belimumab and telitacicept, no significant differences were found in CRR, PRR, or the proportion achieving glucocorticoid tapering targets in the overall population. However, subgroup analyses showed that among patients with high baseline proteinuria (uPCR ≥1500 mg/g), the telitacicept combination group was significantly more likely to achieve CRR than the belimumab combination group (adjusted OR=12.15, 95%CI:1.82-81.01, P=0.010). Sensitivity analyses confirmed that this advantage remained consistent at the cutoff of uPCR ≥2000mg/g (adjusted OR=10.52, 95%CI: 1.06-104.49, P=0.044). Moreover, no obvious interaction was observed between treatment efficacy and baseline disease activity or pathological AI/CI scores. Regarding safety, the incidence of adverse events (AEs) differed significantly among the four groups, whereas the incidence of serious adverse events (SAEs) was comparable.

In the induction treatment of LN, B-cell-targeted biologics combined with standard therapy were superior to traditional immunosuppressive regimens in improving renal response and facilitating glucocorticoid tapering. Belimumab and telitacicept showed comparable efficacy in the overall LN population; however, in patients with higher baseline proteinuria, telitacicept demonstrated a more favorable short-term trend in renal response. Baseline uPCR may serve as an important reference indicator for distinguishing individualized benefit between these two B-cell-targeted strategies.