Abstract / Summary
Abstract Background Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by multisystem involvement and heterogeneous clinical manifestations. Aberrant B-cell activation and elevated levels of B-lymphocyte stimulator (BLyS) play a central role in its pathogenesis [1]. Several B-cell–targeted biologic agents have been developed,however, direct comparative evidence among these therapies remains limited. Objective To systematically evaluate and compare the efficacy and safety of belimumab, rituximab, and telitacicept in patients with SLE or lupus nephritis (LN) using a network meta-analysis. Methods A comprehensive literature search was conducted in PubMed, Embase, Web of Science, the Cochrane Library, as well as the CNKI and Wanfang databases from inception to September 2025. Randomized controlled trials comparing belimumab, rituximab, or telitacicept with placebo plus standard therapy were included. The primary efficacy outcome was the Systemic Lupus Erythematosus Responder Index-4 (SRI-4). A Bayesian network meta-analysis was performed to compare SRI-4 response rates, while safety outcomes, including total adverse events (TAEs) and serious adverse events (SAEs), were assessed using a frequentist framework. Treatment ranking probabilities were estimated using the surface under the cumulative ranking curve (SUCRA). Results Fifteen randomized controlled trials involving 6,455 patients were included. All interventions included in the SRI-4 network demonstrated superior efficacy compared with placebo. Telitacicept had the highest SUCRA ranking for SRI-4 response in the network; however, this probabilistic ranking should not be interpreted as definitive evidence of superior efficacy because the contributing evidence was limited and largely indirect. Belimumab demonstrated consistent efficacy across different dosages and routes of administration, with belimumab 200 mg subcutaneous showing a comparatively favorable balance between efficacy and safety. Rituximab trials did not report SRI-4 responses; however, it did not demonstrate a significant advantage in other evaluated efficacy outcomes, such as British Isles Lupus Assessment Group (BILAG) global scores and 36-Item Short Form Health Survey (SF-36) physical component scores, compared with placebo. Its safety profile was comparable to standard therapy. Conclusions Among B-cell–targeted therapies for SLE, telitacicept appears to offer the greatest efficacy but at the cost of increased adverse events, warranting careful safety monitoring. Belimumab, particularly the 200 mg subcutaneous formulation, provides a favorable risk–benefit profile and may represent a more balanced therapeutic option. For rituximab, the included randomized trials did not demonstrate statistically significant advantages over placebo in the available efficacy outcomes, while the absence of SRI-4 data precluded its inclusion in the primary efficacy network. These findings should be interpreted cautiously and should not be considered evidence of no treatment effect, particularly in selected patients with refractory disease.