Atacicept in primary IgA nephropathy: efficacy, biomarker modulation, and safety - a systematic review and meta-analysis

<p><strong>Background:</strong> IgA nephropathy (IgAN) is a leading cause of chronic kidney disease and kidney failure worldwide, with limited disease specific therapies available. Atacicept, a dual inhibitor of B cell activating factor and a proliferation inducing ligand, targets key immunological pathways involved in disease pathogenesis. This systematic review and meta-analysis evaluated the efficacy and safety of atacicept in patients with IgAN.</p> <p><strong>Methodology:</strong> A systematic search of PubMed, Google Scholar, ScienceDirect, Cochrane Library, and ClinicalTrials.gov was conducted from inception to March 2026. Randomized, double blind, placebo controlled trials in adults with biopsy confirmed IgA nephropathy were included. Data was pooled using a random effects model. Continuous outcomes were analyzed as mean differences (MD) and dichotomous outcomes as risk ratios (RR), each with 95% confidence intervals. Heterogeneity was assessed using the I&sup2; statistic. Subgroup analyses were performed by atacicept dose (25 mg, 75 mg, and 150 mg).</p> <p><strong>Results:</strong> In adults with primary IgAN, three randomized controlled trials (560 participants total) evaluated atacicept against placebo. Atacicept significantly reduced urine protein to creatinine ratio (UPCR) at week 24 (MD &minus;29.04%; p &lt; 0.0001) and week 36 (MD &minus;38.61%; p &lt; 0.0001), with no heterogeneity. Estimated glomerular filtration rate (eGFR) improved significantly at week 36 (MD +8.59 mL/min/1.73 m&sup2;; p = 0.002). Galactose deficient IgA1 (Gd-IgA1) and total immunoglobulin levels were significantly suppressed. The overall adverse event profile was comparable to placebo across all safety endpoints.</p> <p><strong>Conclusion:</strong> Atacicept was associated with improvements in proteinuria, eGFR, and immunological biomarkers compared with placebo, while demonstrating a safety profile comparable to placebo. Because proteinuria and eGFR are surrogate renal endpoints, these findings should be interpreted as evidence of short term biological activity rather than established long term renal benefit. Larger, long term trials evaluating clinically meaningful renal outcomes are needed to define the role of atacicept in clinical practice.</p>