Observation on the Short-Term Efficacy of Telitacicept in the Treatment of Primary IgA Nephropathy

IgA nephropathy (IgAN) ranks among the most prevalent primary glomerulonephritides globally and significantly elevates the risk of chronic kidney disease and end-stage renal disease. Current supportive care, including angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEI/ARB) and sodium-glucose cotransporter-2 inhibitors (SGLT2i), often yields suboptimal outcomes, while corticosteroids and immunosuppressants are limited by safety concerns. Telitacicept is a soluble fusion protein composed of the Fc region of human immunoglobulin G1 (IgG1) fused with the extracellular domain of the Transmembrane Activator and CAML Interactor (TACI). It dual-targets B-lymphocyte stimulator (BLyS) and A Proliferation-Inducing Ligand (APRIL), thereby potentially reducing the production of pathogenic galactose-deficient IgA1 (Gd-IgA1) and intervening in a key upstream event in IgAN pathogenesis. This single-center retrospective study aimed to evaluate the short-term efficacy and safety of Telitacicept in a real-world cohort of patients with primary IgAN.

This study employed a retrospective self-controlled design and included 12 patients with biopsy-confirmed IgAN who were treated with Telitacicept for at least 6 months between January and December 2024. Before enrollment, all patients had maintained at least 3 months of stable background treatment with a combination of ACEI/ARB and SGLT-2i, with well-controlled blood pressure. The primary efficacy endpoint was 24-hour urinary protein excretion（24hUP ）, Secondary endpoints included estimated glomerular filtration rate (eGFR) and urinary red blood cell count. Safety evaluations covered all adverse events recorded during treatment and changes in cardiovascular risk indicators before and after therapy. Statistical analysis was conducted using the Friedman test, followed by the Wilcoxon signed-rank test with Bonferroni correction.

Telitacicept treatment led to a significant reduction in 24hUP at 3 months (P=0.016), with a more pronounced reduction observed at 6 months (P=0.004). The median 24hUP decreased from 1.13 g/24h (IQR 0.62-2.24) at baseline to 0.52 g/24h (IQR 0.26-1.33) at 3 months and was maintained at 0.51 g/24h (IQR 0.15-1.07) at 6 months. The clinical remission rate (defined as 24hUP <0.5 g/24h or a ≥50% reduction from baseline) reached 75.0%. Concurrently, the median eGFR significantly improved from 61.09 ml/min/1.73m² (IQR 35.28-83.16) at baseline to 77.44 ml/min/1.73m² (IQR 39.36-85.63) after 6 months of treatment (P=0.008), with 83.3% of patients showing improved renal function. At the 6-month mark, 70.0% (7/10) of patients who were positive for hematuria at baseline achieved hematuria remission, and the median urinary RBC count significantly decreased from 159.00/μL (IQR 63.50-348.00) to 15.00/μL (IQR 2.50-43.50) (P=0.005). Adverse events were infrequent (4/12 patients) and mild in severity. A significant reduction in non-high-density lipoprotein cholesterol (non-HDL-C) levels was observed (P=0.028), while other cardiovascular risk indicators, including body weight, triglycerides, blood glucose, blood pressure, and uric acid, remained stable.

This real-world study demonstrates that the addition of Telitacicept to standard supportive care over a 6-month treatment period significantly reduces proteinuria, improves renal function, and alleviates hematuria in patients with primary IgA nephropathy, with a favorable safety profile. These findings provide valuable early real-world evidence to support its clinical application