Efficacy, safety, and biomarker changes of B-cell activating factor- and A proliferation-inducing ligand-targeted therapies in IgA nephropathy: A systematic review and meta-analysis of randomized controlled trials

Background: IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide. BAFF (B-cell activating factor) and APRIL (A proliferation-inducing ligand) are cytokines involved in B-cell activation and survival, contributing to the pathogenesis of IgAN. This meta-analysis aimed to evaluate the efficacy, safety, and biomarkers of BAFF and APRIL-targeted therapies in patients with IgAN. Methods: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and was registered with PROSPERO (CRD42024598157). We searched PubMed, Scopus, and the Cochrane Library for randomized controlled trials (RCTs) comparing BAFF or APRIL-targeted drugs with placebo in adults with biopsy-confirmed IgAN. The efficacy outcomes were the mean percent change in the urine protein to creatinine ratio (UPCR) at 24 hours and the mean change in the estimated glomerular filtration rate (eGFR) from baseline. Safety included the incidence of adverse events. The biomarkers were changes in serum Gd-IgA1, IgG, IgA, and IgM from baseline. We used the R software version 4.2.1 for statistics. Results: Four phase II RCTs including 331 patients were included. Compared to placebo, treatment significantly reduced 24-hour UPCR (mean difference [MD] –38.94%; 95% confidence interval [CI] –58.98 to –18.90; p = 0.0001; I² = 0%) and significantly improved eGFR (MD 7.05 mL/min/1.73 m²; 95% CI 3.83 to 10.27; p<0.0001; I²=0%). The incidence of adverse events did not differ significantly in the treatment and placebo groups. The drug significantly decreased serum Gd-IgA1, IgG, IgA, and IgM compared to placebo. Conclusions BAFF and APRIL-targeted therapies effectively and safely reduce proteinuria in patients with IgAN.