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

OBJECTIVES

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.