Combination of Rituximab and Low-dose Tacrolimus in the Treatment of Refractory Membranous Nephropathy: A Retrospective Cohort Study

Background: Conventional regimens for refractory idiopathic membranous nephropathy (IMN) still have limitations. Rituximab (RTX) has a good effect in the treatment of refractory IMN. However, whether RTX single or combined with immunosuppressive therapy is more effective and whether adverse events will increase are still inconclusive. Aims: To investigate the efficacy and safety of RTX combined with low-dose tacrolimus (TAC) versus RTX alone in the treatment of refractory IMN. Study Design: A retrospective cohort study. Methods: We retrospectively studied 91 cases of refractory IMN diagnosed between January 2018 and June 2021, all of which immunosuppressive regimens had failed. Thirty-four patients received RTX combined with TAC (RTX + TAC group), and 57 patients were treated with RTX alone (RTX group). The RTX + TAC group was given RTX 1 g once every 2 weeks, two times, and TAC 0.03 mg/kg/day orally. In the RTX group, RTX was given at the same dosage as the RTX + TAC group. Clinical data were collected at 12 months of follow-up to compare the complete and partial remission rates and the incidence of adverse reactions between the two groups. Results: The overall effectiveness rate of RTX + TAC in the treatment of refractory IMN was 87.14%, of which the partial and complete remission rates were 50.01% and 37.13%, respectively, and the median time to complete remission was 9 (interquartile range [IQR] 6.0, 12.0) months. The overall effectiveness rate of RTX was 65.87%, of which the partial and complete remission rates were 39.48% and 26.39%, respectively, and the median time to complete remission was 10.5 (IQR 6.0, 12.0) months. Adverse events occurred in 6 (17.65%) patients in the RTX + TAC group and in 11 (19.30%) in the RTX group (P = 0.473). Proteinuria and high titer of PLA2R are risk factors for non-remission. Conclusion: The complete and partial remission rates of RTX combined with low-dose TAC in the treatment of refractory IMN are higher than those of RTX alone, and no significant increase in adverse events was noted.