Comparative Efficacy and Safety of Pharmacological Interventions for IgA Nephropathy: A Systematic Review and Meta-Analysis

<i>Background and Objectives:</i> IgA nephropathy represents the most prevalent form of primary glomerulonephritis around the world, with significant heterogeneity in management strategies and outcomes. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of pharmacological interventions for IgA nephropathy. <i>Materials and Methods:</i> We searched multiple databases through June 2025, identifying randomized controlled trials and observational studies evaluating pharmacological treatments in biopsy-proven IgA nephropathy. Primary outcomes included proteinuria reduction and estimated glomerular filtration ration (eGFR) preservation. Secondary outcomes included hard kidney endpoints and safety parameters. Random-effects meta-analyses were performed with comprehensive risk-benefit assessments. <i>Results:</i> Twenty-five studies were included. B-cell/plasma-cell-targeted therapies showed significant proteinuria reduction (-34.0% [95% CI: -45.7, -22.3%]), complement pathway inhibitors demonstrated superior eGFR preservation (+5.8 mL/min/1.73 m²/year [95% CI: 2.4, 9.2]). Systemic corticosteroids showed observed hard outcome benefits (HR 0.37 [95% CI: 0.26, 0.52]) but highest adverse event risk (RR 3.28 [95% CI: 2.11, 5.09]). Novel agents showed projected favorable effects (B-cell: HR 0.38; complement: HR 0.42) pending validation. <i>Conclusions</i>: Novel targeted therapies, especially B-cell/plasma-cell-targeted agents and complement pathway inhibitors, show promising risk-benefit profiles. However, longer-term data and standardized eGFR slope reporting are needed to confirm these findings compared to other immunosuppressive agents.