Timing of treatment-switch to telitacicept in high-risk IgA nephropathy: an observational case series of two clinical scenarios

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. A significant proportion of patients, approximately 20–40%, progress to end-stage renal disease (ESRD) within 10 to 20 years. Telitacicept, a dual inhibitor of BAFF and APRIL, is now recommended in clinical guidelines for the treatment of high-risk IgAN. However, the optimal timing for initiating this therapy remains undefined. This retrospective study included 19 patients with high-risk IgAN (persistent proteinuria of at least 1 g/d despite at least 3 months of optimised therapy, including adequate supportive therapy and conventional anti-inflammatory treatments and/or other immunosuppressants) who received telitacicept. Patients were stratified by the interval from diagnostic kidney biopsy to telitacicept initiation into two groups: <3 years (n = 11) and ≥ 3 years (n = 8). This analysis focused on describing clinical outcomes within each group, aiming to characterise distinct clinical scenarios rather than to perform direct intergroup comparisons. The primary outcome was the change in 24-hour urinary protein levels at 12 months. At the 12‑month follow‑up, reductions in 24-hour urinary protein were observed in both groups. In the < 3 years group (n = 11), median proteinuria decreased from 1.21 g/d (IQR 1.10–1.29) at baseline to 0.17 g/d (IQR 0.10–0.34). The overall efficacy rate (complete or partial remission) was 54.5% (6/11). In the ≥ 3 years group (n = 8), median proteinuria decreased from 2.36 g/d (IQR 1.85–2.75) to 1.01 g/d (IQR 0.64–1.89). The overall efficacy rate was 37.5% (3/8). No serious adverse events were reported. In this descriptive case series of patients with high-risk IgAN, telitacicept was associated with proteinuria reduction and stable renal function over 12 months. Median proteinuria reduction was 84% in patients initiating treatment earlier (< 3 years from biopsy) and 50% in those starting later (≥ 3 years). These observations are descriptive and, given the small sample and baseline imbalances, should be interpreted with caution. These preliminary observations may inform clinical decision-making and highlight treatment timing as a question warranting further investigation in larger prospective studies.