Efficacy and safety of low-dose telitacicept in IgA nephropathy: a real-world study

Abstract Background IgA nephropathy (IgAN) represents one of the most common causes of primary glomerulonephritis with unmet clinical needs. This study evaluates the efficacy and safety of telitacicept in patients with IgAN. Methods This real-world study included 38 biopsy-proven IgAN patients with baseline estimated glomerular filtration rate (eGFR) > 10 mL/min/1.73 m² and urine protein-to-creatinine ratio (UPCR) > 440 mg/g. Nineteen patients received weekly telitacicept 80mg (telitacicept group), divided into early-start (telitacicept treatment initiated within 6 months after diagnosis) and late-start (>6 months) subgroups. The other 19, diagnosed during the same period but not receiving telitacicept, served as controls. Clinical data were collected over 12 months. Safety was evaluated. Results Baseline characteristics were comparable between groups. In the telitacicept group, median UPCR was 1715.98 mg/g (IQR: 1281.63–2892.11) and median eGFR was 45.45 mL/min/1.73 m² (IQR: 33.86–93.14). Over 12 months, telitacicept 80 mg weekly was associated with a trend toward greater proteinuria reduction (−51.52% versus − 33.31%, P = .081) and a favorable change in renal function (+1.77 versus -4.06 mL/min/1.73 m², P = .008). The early-start subgroup showed greater benefits than the late-start subgroup. In an exploratory analysis of patients with eGFR below 35 mL/min/1.73 m² (n = 7 each), telitacicept treatment yielded a sustained reduction in UPCR (−48.83% versus + 9.68%) and a stable mean annualized eGFR slope (+0.77 versus − 8.88 mL/min/1.73 m²) over 12 months. No severe adverse events occurred with telitacicept, versus one in controls. Conclusions Our study supports the potential efficacy of low-dose telitacicept in reducing proteinuria and stabilizing eGFR in IgAN. Its clinical benefits were more pronounced when initiated early after diagnosis. Furthermore, in IgAN patients with severe renal impairment, telitacicept may yield better outcomes for proteinuria reduction and eGFR preservation than conventional treatment. These advantages position low-dose telitacicept as a potentially effective treatment strategy, though larger prospective studies are warranted.