Effects of telitacicept and belimumab on systemic lupus erythematosus: a systematic review and meta-analysis

B cell-targeted therapies play an important role in systemic lupus erythematosus (SLE). Belimumab targets B lymphocyte stimulator (BLyS), whereas telitacicept inhibits both BLyS and APRIL. Although both drugs have demonstrated clinical efficacy in SLE, comparative benefits and risks of telitacicept versus belimumab remain unclear. We performed a systematic review and meta-analysis using indirect comparisons to compare their efficacy and safety. We searched 6 database for randomized controlled trials (RCTs) published up to November 1, 2025, without language restriction. Trials evaluating belimumab or telitacicept in adult SLE patients were included. Primary outcomes included SLE Responder Index 4 (SRI4), SRI7 response rates and decreasing SLEDAI score. Secondary outcomes included prednisone dose reduction, anti-dsDNA change, adverse events (AEs) and serious AEs. Data extraction and risk-of-bias assessment were performed independently by two reviewers. Analysis used RR with 95% CI, and heterogeneity was assessed by I ² . Sensitivity, subgroup and publication-bias analyses were performed. 11 trials with telitacicept and belimumab involving 4303 participants were included. Compared with the belimumab group, telitacicept significantly increased the SRI4 response rate (relative risk [RR], 2.03, 95%CI, 1.65–2.49, p  < 0.0001), SRI7 response rate (RR, 3.61, 95%CI, 1.57–8.29, p  = 0.002) and decreased SLEDAI score (RR, 1.67, 95%CI, 1.41–1.97, p  < 0.0001). Compared with belimumab, telitacicept exhibited a significant advantage in SRI4 response rate (p for interaction = 0.0002), without a significant difference in adverse events. Certainty of evidence ranged from moderate to high, but heterogeneity was present for some outcomes. Telitacicept improved SRI4 and SRI7 response rates, reducing disease activity and prednisone dosage, without a clear increase in infection risk compared with belimumab. Dual inhibition of BLyS and APRIL by telitacicept may offer an effective option for reducing SLE activity. Further large-scale, long-term head-to-head trials are needed to confirm these findings.