Comparison of the Efficacy of Rituximab and Tacrolimus in Patients with High-Titer Phospholipase A2 Receptor (PLA2R) Antibody-Associated Membranous Nephropathy

Background: This study aimed to analyze the remission rate of rituximab and tacrolimus in patients with high-titer anti-PLA2R antibodies associated membranous nephropathy. Methods: Patients diagnosed with membranous nephropathy by positive anti-PLA2R antibodies and the level >100 RU/ml at diagnosis, with or without renal biopsy, from January 2018 to April 2023, were enrolled. A total of 188 patients were enrolled according to different treatment regimens and were divided into the rituximab group (RTX group, n = 49), the tacrolimus group (TAC group, n = 102), and the rituximab combined with tacrolimus group (RTX+TAC group, n = 37). The clinical responses of the patients were analyzed. Results: After 12 months of follow-up, 85.7% patients in the RTX group, 75.7%patients in the RTX+TAC group and 61.8% patients in the TAC group achieved total remission. During follow-up, 14.7% of patients in the TAC group developed end-stage renal disease, and survival curves showed significant differences in total and partial remission rates among the three groups (p=0.015) Conclusion: Rituximab was superior to tacrolimus regarding total remission rate in patients with high-titer PLA2R antibody. These findings reinforce RTX's position as a first-line therapy for iMN, particularly advantageous for patients at high risk of disease progression.Fig 1. TotalRemission rate for iMN patients in three groups at 12M. Baseline characteristics of patients with high titer anti-PLA2R antibody IMN in three groups - TAC（N=102） RTX（N=49） RTX+TAC (N=37) P value Gender, male/female 65/37 36/13 21/16 0.257 Age, year 57.83±12.38 54.39±15.88 52.89±13.82 0.114 Level of anti，PLA2R Ab, RU/mL 189.05（127.78，374.18） 195.39（150.89，382.39） 247.46（130.65，383.01） 0.670 Proteinuria, g/24h 5.80（3.76，7.61） 7.55（4.61，12.20） 6.16（4.01，9.62） 0.007 eGFR, mL/min/1.73m2 78.34（62.75，98.91） 71.93（53.23，98.48） 74.76（55.83，74.76） 0.408 eGFR: estimated glomerular filtration rate; RTX: Rituximab; TAC: Tacrolimus