Calcineurin inhibitor combined with Rituximab is superior to combined with glucocorticoids or RTX alone in the treatment of IMN：A retrospective study
Authors: Sun Xiang long , Wang Jian ying , Fan Kai li , Yin Fang , Qin Li li , Su Li jie , Sun Jing shu , Xu Yue , Zhang Kun ying 
Published: February 2024

BACKGROUND Studies demonstrate that T cells secrete interleukin and other cytokines to promote the growth and activation of B cells, and B lymphocytes release antibodies that attach to the PLA2R and THSD7A surface antigens on podocytes to create immunological complexes that are deposited beneath the glomerular epithelium, which damage the filtration barrier and trigger proteinuria.The combination regimen of Calcineurin inhibitors（CNIs）and rituximab(RTX) could simultaneously inhibit the proliferation of T and B lymphocytes and reduced the production of immune complexes.This kind of therapeutic method for idiopathic membranous nephropathy may achieve better clinical results and less complications. METHODS Fifty-eight patients who were diagnosed as idiopathic membranous nephropathy（IMN）through a biopsy suffering from nephrotic syndrome (NS) were recruited, and were divided into RTX treatment group(RTX group), CNIs combined with RTX treatment group(CNIs+RTX group) and CNIs combined with glucocorticoids(GC) treatment group(CNIs+CG group) according to their treatment background. All patients in 3 groups were followed up for at least 12 months. Clinical composite remission(including complete or partial remission) at 12 months was the main result; safety and the incidence of adverse events were the secondary outcomes. RESULTS The PLA2R antibody level of RTX+CNIs group at the baseline much higher than RTX and CNIs+GC groups (240.30(84.56,386.99)RU/ml vs. 44.94(11.48,143.94)RU/ml, 7.72(2.00,102.68) RU/ml, respectively, p=0.006). The PLA2R antibody concentrations among the three groups become comparable at the end of 3 months(36.80(2.10,88.05) RU/ml vs.14.32(2.00,47.98)RU/ml, 2.60(2.00,24.50) RU/ml, respectively, p&gt;0.05). At 12 months, all patients in the CNIs+GC group achieved immune remission, and the PLA2R-ab concentration was less than 14RU/ml. At 3 months, 33of 58 patients(56.90%) had a composite remission(complete or partial remission), including 4 of 14 patients (27.85%) in the RTX group, 11 of 17 patients(64.71%) in the CNIs+RTX group and 18 of 27 patients (66.67%) in the CNIs+GC group (p=0.048). At 12 months, 51 of 58 patients(87.93%) had a composite remission, including 12 of 14 patients (85.71%) in the RTX group, 15 of 17 patients(88.24%) in the CNIs+RTX group and 24 of 27 patients (88.89%) in the CNIs+GC group (p=0.957). During the 12-month study, 7 patients did not response for the treatment. 1 patient relapsed during the 12-month treatment with a re-elevation of antibodies. Adverse events occurred in 18(31.03%)patients in the whole study, including 3 patients(5.17%) in the RTX group, 2 patients(3.45%) in the CNIs+RTX and 13patients(22.41%) in the CNIs+GC group(p&lt; 0.05). CONCLUSIONS The combination of CNIs and RTX can effectively alleviate idiopathic membranous nephropathy with nephrotic syndrome in the first 3 months，as well as the combination of CNIs and GC, and the efficacy of both treatment methods for IMN was superior to that of RTX alone at the first 3 months. Furthermore, the RTX+CNIs group had less side effects compared with GC+CNIs group. So CNIs combined with RTX could be recommended as a superior therapeutic method for IMN treatment to shorten remission durion with less complications.