Short-Term Efficacy and Safety of Telitacicept in Advanced IgA Nephropathy (Lee's Grade IV-V): A Case Series of 6 Patients

IgA nephropathy (IgAN) is the most common primary glomerulonephritis in the Asia-Pacific region. Patients with Lee's grade IV-V disease exhibit severe pathological changes, typically characterized by proliferative sclerotic lesions and a poor prognosis. The management of advanced IgAN remains challenging, as a subset of patients responds inadequately to or cannot tolerate conventional immunosuppressive regimens. The 2025 KDIGO guidelines highlight the necessity of targeted disease-modifying therapy for high-risk individuals. Telitacicept is a novel biologic agent that dually neutralizes BLyS and APRIL, thereby reducing the production of pathogenic IgA1 at its source. Nevertheless, real-world evidence regarding its efficacy, particularly the early treatment response in patients with severe pathology, remains limited and requires further accumulation. This study aims to evaluate the short-term efficacy and safety of Telitacicept in patients with biopsy-proven Lee's grade IV-V IgAN.

We conducted a single-center, retrospective observational study of 6 patients with biopsy-proven IgAN (Lee's grade IV-V) who commenced Telitacicept treatment at the First Hospital of Jilin University between December 2023 and December 2024. The study was designed to reflect real-world practice; therefore, no restrictions were placed on prior treatment history. The primary endpoint was the change in 24-hour urinary protein excretion (24hUPRO) from baseline to 6 months. Secondary endpoints included changes in estimated glomerular filtration rate (eGFR), rates of complete remission (CR), partial remission (PR), and total remission (TR), as well as safety. Statistical analyses were performed using SPSS 27.0. Continuous variables were tested for normality; paired t-test or Wilcoxon signed-rank test was applied for comparisons between baseline and 6-month data as appropriate.

Baseline Characteristics: The cohort had a mean age of 36 ± 13 years, and 66.7% (4/6) were male. At baseline, the mean 24hUPRO was 5.1 ± 2.4 g/24h, and the mean eGFR was 47 ± 21 mL/min/1.73m².Efficacy Outcomes:Proteinuria: After 6 months of Telitacicept treatment, mean 24hUPRO significantly decreased to 1.4 ± 0.8 g/24h, corresponding to a mean reduction of 72.3 ± 12.8% from baseline (p=0.007). The mean absolute reduction was 3.7 ± 2.1 g/24h.Renal Function: Mean eGFR at 6 months was 55 ± 21 mL/min/1.73m², showing no significant decline from baseline (p=0.131).Remission Rates: At the 6-month endpoint, CR was achieved in 16.7% (1/6) of patients, and PR was achieved in 83.3% (5/6), resulting in a TR rate of 100% (6/6). Safety Profile: All patients completed the 6-month follow-up. Treatment was well-tolerated, with no reports of serious infections (e.g., pneumonia), significant injection site reactions, or other treatment-related adverse events.

In this small case series of patients with high-risk, advanced IgAN (Lee's grade IV-V), Telitacicept treatment over 6 months was associated with a significant reduction in proteinuria and stabilization of renal function, demonstrating a favorable safety and tolerability profile. These findings provide initial real-world evidence from the Asia-Pacific region supporting the use of Telitacicept in this difficult-to-treat population, aligning with the treatment goals endorsed by the 2025 KDIGO guidelines. The promising results warrant further investigation through longer-term follow-up and larger prospective studies.