Efficacy and Safety of Low-Dose Telitacicept in Patients with Primary IgAN

Background: Preliminary phase II trial data suggested the proteinuria-lowering potential of telitacicept (160mg or 240mg per week) in IgA nephropathy (IgAN). This study evaluates low-dose telitacicept (80 mg/week) in IgAN to establish its efficacy and safety profile. Methods: This study recruited biopsy-proven IgAN patients with 24-hour proteinuria >0.5 g/day or UPCR >500 mg/g. 13 patients receiving low-dose telitacicept (80 mg qw) constituted the telitacicept group, with a matched concurrent control group receiving immunosuppressive (IS) therapy designated as the IS group. In the Telitacicept group, a subset of cases combined with low-dose hydroxychloroquine or other non-corticosteroid IS agents. 5 patients in the telitacicept group exhibited severe renal impairment (eGFR <35 mL/min/1.73 m^2), a population excluded from the prior phase II clinical trial. A mixed-effects model for repeated measures analysis was used to assess the change from baseline over time for UPCR and eGFR. Results: The median follow-up duration was 253 and 237 days for the telitacicept and IS groups. Sustained and consistent proteinuria reductions were demonstrated in the telitacicept group throughout the study (p = 0.001). At 8 months, UPCR change from baseline was -54.64% ± 13.77%, compared with -36.9% ± 15.80% in the IS group, despite no statistical difference (p=0.250). During an 8-month observation, telitacicept demonstrated superior renal protection (p=0.038) with preserved eGFR change from baseline (0.37 ml/min/1.73 m^2) compared with -1.43 ml/min/1.73 m^2 in the IS group. However, in patients with severe renal impairment, the eGFR change did not reach significance between the two groups(p=0.381). No serious adverse events were observed in the telitacicept treatment group. Blood IgG decrease (4/13) was the most common investigator-assessed treatment-related adverse event in the Telitacicept group Conclusion: Low-dose telitacicept can reduce proteinuria in a safety profile in IgAN patients. Telitacicept treatment showed superior kidney protection efficacy compared with IS agents during the 8-month follow-up. Funding: Government Support – Non-U.S.