Background: IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. A Proliferation-Inducing Ligand (APRIL) plays a critical role in the development and progression of IgAN. This study aimed to evaluate the efficacy and safety of sibeprenlimab, an APRIL receptor antagonist, in IgAN patients.
Methods: A comprehensive literature search was conducted in PubMed, Embase, Web of Science, and Cochrane Library from database inception to November 30, 2025. Randomized controlled trials (RCTs) were identified. Literature quality was assessed using the Cochrane Risk of Bias 2 tool. Data were analyzed using RevMan 5.4.
Results: Two high-quality, multi-center, double-blinded RCTs involving 665 primary IgAN patients were included. Compared with the control group, the sibeprenlimab group showed a greater percentage reduction in urine protein-to-creatinine ratio (UPCR) (MD -48.35, 95% CI -62.00 to -34.69, P < 0.00001), a lower proportion of patients experiencing hematuria (OR 0.11, 95% CI 0.06 to 0.20, P < 0.00001), a lower least-squares mean change in estimated glomerular filtration rate (eGFR) (MD 6.11, 95% CI 2.06 to 10.16, P = 0.003), and a marked decrease in circulating galactose-deficient IgA1 (Gd-IgA1) and serum APRIL levels (mean reductions of 66.0% and 95.8%, respectively). Although the overall incidence of adverse events was comparable (OR 0.90, 95% CI 0.39 to 2.09, P = 0.80), the sibeprenlimab group experienced a greater reduction in serum IgG, IgA, and IgM levels than the control group (mean reductions of 35.0%, 66.5%, and 74.8%, respectively).
Conclusions: Current limited but robust evidence suggests that sibeprenlimab is effective in reducing proteinuria and hematuria, lowering circulating Gd-IgA1 and serum APRIL levels, and slowing the decline in eGFR in IgAN patients. Although sibeprenlimab exhibits an overall favorable safety profile, it may be associated with reductions in serum IgG, IgA, and IgM levels.
Clinical trial number: Not applicable.
Supplementary Information: The online version contains supplementary material available at 10.1186/s12882-026-04927-9.
Keywords: A proliferation-inducing ligand; IgA nephropathy; Meta-analysis; Randomized controlled trial; Sibeprenlimab.