Efficacy and safety of BAFF/APRIL dual antagonists in IgA nephropathy: a systematic review and meta-analysis of randomized controlled trials

Le résumé fourni par la source

BACKGROUND: IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Dysregulation of cytokines B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) signaling pathway is associated with multiple core pathogenesis of IgAN patients and the elevation levels of serum BAFF and APRIL are positively correlated with the severity of the disease in IgAN patients. This study aimed to comprehensively evaluate the efficacy and safety of BAFF/APRIL dual antagonists in IgAN patients. METHODS: Literature search was performed using PubMed, Embase, Web of Science, Scopus and Cochrane Library from inception to 28 February 2025. All randomized controlled trials (RCTs) were identified. Data analysis was conducted using RevMan 5.4. RESULTS: Three Phase Ⅱ double-blind RCTs involving 263 primary IgAN patients were included. Compared with the control treatment, BAFF/APRIL dual antagonists achieved a greater percentage decrease from baseline in urine protein-to-creatinine ratio (UPCR) [mean difference (MD) -36.67, 95% confidence interval (CI) -40.31 to -33.03] and circulating galactose-deficient IgA1 (Gd-IgA1) (MD -45.55, 95% CI -61.33 to -29.78), while led to a greater increase from baseline in estimated glomerular filtration rate (eGFR) (MD 9.65, 95% CI 7.73 to 11.57). However, BAFF/APRIL dual antagonists were associated with a higher risk of injection site reactions [odds ratio (OR) 30.94, 95% CI 6.43 to 148.75] and greater percentage decrease from baseline in serum IgG (MD -22.65, 95% CI -33.83 to -11.48), IgA (MD -41.41, 95% CI -55.35 to -27.48) and IgM (MD -63.39, 95% CI -77.29 to -49.50). CONCLUSION: Based on the currently limited evidence, we cautiously conclude that BAFF/APRIL dual antagonists may reduce the levels of 24-hour UPCR and circulating Gd-IgA1 in patients with IgAN, while concomitantly delay the decline of eGFR. However, it should be noted that BAFF/APRIL may cause injection site reactions. More importantly, BAFF/APRIL dual antagonists may reduce the levels of serum IgG, IgA and IgM, potentially weakening the immune function of patients.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.