#877 Efficacy and safety of telitacicept in IgA nephropathy: a preliminary report of the large single-center observational study

Abstract Background and Aims IgA nephropathy (IgAN) is a common type of primary glomerulonephritis worldwide with nearly 40% of patient progresses to end-stage renal disease (ESRD) in 10-20 years. The most widely accepted hypothesis is known as the ‘multihit hypothesis’. B cells play an important role in producing galactose-deficient IgA1 (Gd-IgA1) and its autoimmune antibody, resulting in the deposition of IgA in the mesangium. B-cell activating factor (BAFF), also known as B-lymphocyte stimulator (BLyS), and a proliferation-inducing ligand (APRIL) have been reported to play crucial roles in the activation of B lymphocytes. Telitacicept, a soluble humanized recombinant fusion protein that effectively neutralizes the activity of BLyS and APRIL had been demonstrated the ability to reduce proteinuria with adverse events similar to supportive care in a phase 2 clinical trial. Therefore, our project was aiming to conduct a large single-center observational study to explore the efficacy and safety of telitacicept in patients with IgAN compared with supportive therapy and glucocorticoid therapy. Method We are aiming to conduct a observational study of adults who had undergone renal biopsy at the First Hospital of Jilin University between October 2023 and December 2026 and were diagnosed with IgAN. Up to now, out of the initial pool of 243 patients, 159 were excluded based on specific criteria: (1) eGFR (CKD-EPI) <35 mL/min/1.73 m² (n = 39); (2) proteinuria <0.5 g/d (n = 10); (3) others (n = 109). So far, 84 eligible IgAN patients were enrolled in the project and 64 IgAN patients can be analysed due to the fllowed-up time. All patients received supportive care and were taking the maximally tolerated dose of angiotensin receptor blockers. The patients were divided into four groups according to the therapy: telitacicept (Group A, not enough cases now), telitacicept combined low-dose corticosteroids (Group B, n = 20), adequate-dose of glucocorticoids (Group C, n = 21) and angiotensin receptor blockers (Group D, n = 23). The efficacy was defined as a decrease in proteinuria of 50% or more. The research protocol underwent thorough scrutiny and received approval from the ethical committees of the First Hospital of Jilin University (approval number: 2024-1165). Results A cohort of 64 patients with IgAN were recruited with a follow-up duration of 12 weeks. All the clinical data has no significance among Group B, C and D. The median baseline proteinuria of Group B, C, D was 1.85 g/day, 1.34 g/day and 1.26 g/day respectively, while median baseline eGFR was 62.98 mL/min/1.73 m2, 82.26 mL/min/1.73 m2 and 78.44 mL/min/1.73 m2. Patients with higher proteinuria and lower eGFR are more likely to choose telitacicept. Renal biopsy data showed significance in T classification. The total efficacy among the three group also has no significance. Figure 1 showed the changing process of proteinuria and eGFR at week 4, week 8 and week1, indicates that telitacicept combined low-dose corticosteroids can reduce proteinuria and stabilize eGFR in patients with IgAN. However the adequate-dose of glucocorticoids seemed to keep urine protein at a lower level than telitacicept within 12 weeks, the long follow-up of our project may give the answer later. Conclusion Telitacicept can reduce the dose of corticosteroids and is no inferior to corticosteroid therapy in IgAN, the long-term kidney protection still needs to be confirmed.