Clinical efficacy and safety of rituximab with membranous nephropathy: a meta-analysis

Membranous nephropathy (MN) is an organ-specific autoimmune disease, and its prevalence is increasing. B lymphocytes activated by T cells produce antibodies. CD19+/CD20+ plasma cells may contribute to autoantibody and alloantibody production. Rituximab has been effective in treating MN in many clinical trials. Thus, we conducted a meta-analysis to explore the clinical efficacy and safety of rituximab with MN.

We searched Embase, PubMed, Cochrane Library and ClinicalTrials.gov without language or publication date limitations. Studies were classified in high-risk, medium-risk and low-risk groups based on baseline proteinuria. Follow-up periods and different administrations of rituximab were also compared. Complete remission (CR) and partial remission (PR) were assessed to measure the efficacy of rituximab, and adverse effects were also extracted. Dichotomous data were expressed by the odds ratio (OR), and the 95% confidence intervals (95% CI) were used for the recruited studies.

Fourteen articles, including 17 studies, were included in this meta-analysis. The pooled OR of overall PR and CR remission rate was 0.58 (95% CI: 0.53-0.63; p = 0.003). No studies belonged to the low-risk group. The overall PR and CR remission rate in the medium-risk group was 0.56 (95% CI: 0.36-0.73; p = 0.57). The pooled OR of overall PR and CR remission rate in the high-risk group was 0.59 (95% CI: 0.53-0.65; p = 0.03). At the 12-month follow-up, the pooled OR of overall PR and CR remission rate was 0.51 (95% CI: 0.43-0.59; p = 0.72). At the 24-month follow-up, the pooled OR of overall PR and CR remission rate was 0.71 (95% CI: 0.48-0.86; p = 0.07). The pooled OR of efficacy of rituximab at 375 mg/m² × 4 was 0.63 (95% CI: 0.55-0.70; p = 0.001). Rituximab was tolerated in MN, and most adverse effects were mild. The pooled OR of infusion reaction rate of rituximab was 0.25 (95% CI: 0.13-0.44; p = 0.01) in MN. The pooled OR of cardiovascular-related event rate of rituximab in MN was 0.04 (95% CI: 0.02-0.11). The pooled OR of infection rate of rituximab in MN was 0.06 (95% CI: 0.03-0.12; p < 0.00001).

Rituximab is safe and effective in MN and a promising alternative treatment. More randomized control trials and studies on the role of MN are expected.