Efficacy and Safety of Telitacicept Combined with Immunosuppressive Therapy for IgA Nephropathy: A Retrospective Multicenter Cohort Study

APRIL and BAFF inhibition has shown promise as a therapeutic option for immunoglobulin A nephropathy (IgAN). However, the efficacy of combining APRIL and BAFF inhibitors with immunosuppressants remains unknown. To investigate this, we conducted a retrospective, real-world study comparing the efficacy and safety of telitacicept combined with glucocorticoids/mycophenolate mofetil (GM) to telitacicept monotherapy in the treatment of IgAN.

A multicenter retrospective cohort study was conducted among 228 patients who were diagnosed IgAN and treated with telitacicept between April 2023 and July 2024. Participants were categorized into two groups based on their treatment regimens: the telitacicept group (n = 113) and the telitacicept + GM group (n = 115, Fig. 1). Clinical data were collected from the initiation of treatment up to a 9-month period. The primary endpoints were 24-hour proteinuria and estimated glomerular filtration rate (eGFR). The Kaplan-Meier method was employed to compare the complete remission rate and overall remission (complete + partial) between the two groups. Cox regression model was utilized to analyze the association between different treatment regimens and complete remission rate. Furthermore, subgroup analyses were conducted, and the results were depicted in a forest plot.

The study included 228 patients with a mean age of 39.7 ± 11.5 years, of whom 86 (37.7%) were male. Baseline characteristics were well balanced between the groups (Table 1). Significant differences in proteinuria between the groups were observed at both 6 months (0.6 vs. 0.3 g/day, P < 0.001) and 9 months (0.3 vs. 0.2 g/day, P = 0.001, Fig. 2a). At 9 months, telitacicept + GM demonstrated a significantly greater reduction in proteinuria (-85.4% vs. -75.6%, P = 0.001, Fig. 2b). In terms of renal function, eGFR exhibited slight improvement, with a more pronounced effect observed in the telitacicept + GM group compared to the telitacicept group (70.8 vs. 61.5 mL/min/1.73 m², P = 0.036, Fig. 2c-d). Although the two groups showed similar reductions in urinary red blood cell (RBC) count over 9 months (Fig. 2e), the telitacicept + GM group experienced a significantly greater reduction, with a median change of −35.5/μL (IQR −88.3 to −6.0/μL), compared to −9.0/μL (IQR −39.0 to 0.0/μL) in the telitacicept group at 9 months (P = 0.009, Fig. 2f). Kaplan-Meier analysis indicated higher complete remission rate (61.7% vs. 45.1%; P = 0.012, Fig. 3a) and overall remission rate (86.1% vs. 75.2%; P = 0.038, Fig. 3b) in the telitacicept + GM group at 9 months. After adjusting for various factors, multivariable Cox regression revealed that the telitacicept + GM regimen was associated with a significantly higher likelihood of achieving complete remission at 9 months [adjusted HR 2.58 (95% CI 1.65-4.04), Table 2]. Subgroup analysis revealed consistent benefits of the telitacicept + GM regimen across all predefined subgroups, with no significant interaction effects detected (all P for interaction ≥ 0.05, Fig. 4). Although the telitacicept + GM group was associated with a higher overall incidence of adverse events (35.7% vs. 12.4%, P < 0.001, Table 3), no serious adverse events were reported in either group.

Telitacicept + GM regimen significantly reduced proteinuria and hematuria in IgAN patients, without any occurrence of serious adverse events.