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

Abstract

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.

Figure 1

Flow chart of the trial. The flowchart shows the patient selection process in this retrospective cohort study. The cohort included 107 patients with refractory membranous nephropathy between January 2018 and November 2021. After screening under the conditions shown in this figure, 91 eligible patients (RTX + TAC group, n = 34; TAC group, n = 57) were included in the final analysis.

Figure 2

Changes in indices in the two groups during follow-up. Changes in the levels of 24-h proteinuria (a), serum albumin (b), eGFR (c), anti-PLA2R (d) in the two groups at baseline and during follow-up. The two groups were compared at different time points (ns, no significant difference, *P < 0.05, **P < 0.01, P < 0.05 indicates significant difference).

Figure 3

Partial remission rate and complete remission rate of the RTX and RTX + TAC groups during the follow-up. (a) Partial remission rates of the two groups. The partial remission rates of the RTX + TAC and RTX groups were 50.01% and 39.48%, respectively, at 12 months (P = 0.019). (b) Complete remission rates of the two groups. The complete remission rates of RTX + TAC and RTX groups were 37.13% and 26.39%, respectively, at 12 months (P = 0.037).