Efficacy and safety of telitacicept for rituximab-refractory membranous nephropathy.

BACKGROUND: Rituximab (RTX) is the first-line treatment for primary membranous nephropathy (MN), but 30-40% of patients are refractory. Persistent activation of the BAFF/APRIL pathway underlies RTX resistance. Telitacicept, a dual BAFF/APRIL inhibitor, may offer a novel therapeutic approach. METHODS: This retrospective study included 11 patients with RTX-refractory primary MN who received weekly subcutaneous telitacicept (160 mg) and were followed for ≥6 months. Primary endpoint was proteinuria remission rate at 6 months. Secondary endpoints included anti-PLA2R antibody levels, renal function, and safety. RESULTS: Mean age was 49.5 years; 63.6% were male. After 6 months, objective response rate was 63.6% (27.3% complete remission, 36.4% partial remission). In the whole cohort, 24-h urine protein decreased from 7.89 ± 2.84 to 2.91 ± 2.66 g/day (P = 0.004); serum albumin increased from 25.32 ± 4.01 to 31.92 ± 8.35 g/L (P = 0.010). In the 7 patients who achieved remission, 24hUP decreased from 8.45 ± 3.50 to 1.28 ± 1.20 g/day (P = 0.003) and serum albumin increased from 26.24 ± 4.21 to 36.69 ± 6.45 g/L (P = 0.002). Anti-PLA2R antibodies declined from 47.44 (32.36-98.32) to 7.25 (1.65-26.30) RU/mL (P = 0.001), with 45.5% achieving immune remission; antibody rebound between 3 and 6 months was observed in 5 patients, 4 of whom had a dose reduction. Renal function remained stable (eGFR 65.2 ± 20.6 to 61.5 ± 16.9 mL/min/1.73 m2; P = 0.137). Four patients (36.4%) experienced mild to moderate adverse events; no serious events occurred. CONCLUSION: Telitacicept demonstrates favorable efficacy and acceptable safety in RTX-refractory MN, representing a promising treatment option for this challenging population.