Efficacy and safety of BAFF/APRIL-pathway inhibitors versus placebo in adults with IgA nephropathy: a systematic review with pairwise and network meta-analysis
Abstract
Background: B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) drive the galactose-deficient IgA1 (Gd-IgA1) production that underlies IgA nephropathy (IgAN). Several BAFF/APRIL-pathway inhibitors have entered randomized testing, but none has been compared head-to-head.
Methods: We systematically searched MEDLINE, Scopus, the Cochrane Central Register, Web of Science, and Embase to July 2026 for randomized, placebo-controlled trials of BAFF/APRIL-pathway inhibitors in adults with biopsy-proven IgAN. Random-effects pairwise meta-analysis used the standardized mean change for proteinuria and estimated glomerular filtration rate (eGFR), change-score standardization for biomarkers, and risk ratios (RR) for safety, and a frequentist star network meta-analysis with placebo as reference ranked agents by P-score.
Results: Seven trials (1,590 adults) evaluating telitacicept, atacicept, and sibeprenlimab were included. Versus placebo, BAFF/APRIL-pathway inhibition reduced proteinuria (SMCR -0.73, 95% CI -0.88 to -0.58, p 2 = 0%) and a small difference in eGFR favouring active treatment (+0.21, 95% CI 0.04 to 0.38, p = 0.016, I2 = 0%). Serum Gd-IgA1 and total IgA fell substantially but with high heterogeneity (I2 > 95%). Serious adverse events (RR 0.52, 95% CI 0.30 to 0.90) and treatment discontinuations (RR 0.31, 95% CI 0.11 to 0.88) were fewer with active treatment, overall adverse events did not differ (RR 1.03, 95% CI 0.92 to 1.16), and injection-site…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 1,590 participants or records.
Read the paper
Related studies
- Comparative effectiveness of GLP-1 receptor agonists on glycaemic control, body weight, and lipid profile for type 2 diabetes: systematic review and network meta-analysis
- Adverse effects of cyclooxygenase 2 inhibitors on renal and arrhythmia events: meta-analysis of randomized trials
- Benefits and harms of drug treatment for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials
- Comparative effectiveness and safety of statins as a class and of specific statins for primary prevention of cardiovascular disease: A systematic review, meta‐analysis, and network meta‐analysis of randomized trials with 94,283 participants
- Screen time increases overweight and obesity risk among adolescents: a systematic review and dose-response meta-analysis
- Exposure to WHO AWaRe antibiotics and isolation of multi-drug resistant bacteria: a systematic review and meta-analysis
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.