BAFF/APRIL-targeted therapy for systemic lupus erythematosus and lupus nephritis: a systematic review and meta-analysis.

The objective of this study is to systematically evaluate the organ-specific efficacy and safety of six BAFF/APRIL-targeted therapies in Systemic Lupus Erythematosus (SLE) and Lupus Nephritis (LN), and to construct the first organ-specific evidence map identifying research gaps across six clinical domains. PubMed, Cochrane CENTRAL, Embase, Web of Science, registries and Chinese databases were searched through June 2026 for adult Phase II/III RCTs. Primary quantitative outcomes were SRI-4 response and complete renal response. Random-effects models calculated risk ratios (RRs). Primary syntheses used verifiable full-text data; limited-source datasets were retained only for qualitative or sensitivity analyses. RoB 2 and GRADE were applied, and an evidence map visualized gaps. Eighteen independent RCTs were included; 13 contributed quantitative data, and five were retained for qualitative synthesis only. For SRI-4 response, belimumab showed RR 1.29 (95% CI, 1.17-1.42; three trials, n = 1961), telitacicept RR 1.96 (95% CI, 1.61-2.38), and tabalumab RR 1.21 (95% CI, 1.09-1.34; two trials, n = 2281 in the modified-SRI analysis). In LN, the full-text primary estimate from BLISS-LN was RR 1.52 (95% CI, 1.13-2.05); an all-source sensitivity analysis yielded RR 1.44 (95% CI, 1.14-1.83; three datasets). Serious adverse events showed RR 0.98 (95% CI, 0.87-1.11). GRADE yielded one moderate-certainty, two low-certainty, and three very low-certainty outcomes. Available evidence suggests that several BAFF/APRIL-targeted therapies may improve SRI-4 response in SLE, with belimumab supported by the most mature evidence base. Renal benefit is established primarily by BLISS-LN, while evidence for other agents remains uncertain. Findings should be interpreted cautiously because most outcomes were supported by low or very low certainty evidence. Key Points • BAFF/APRIL-targeted therapies may improve SRI-4 response in SLE, although certainty varies substantially across agents and outcomes. • Belimumab has the most mature evidence base, whereas telitacicept shows a promising efficacy signal that requires broader confirmation; no evidence of increased serious adverse-event risk was observed. • The organ-specific evidence map identifies seven important research gaps and should be interpreted alongside the predominantly Low or Very low certainty of evidence.