Treatment of Idiopathic Membranous Nephropathy for Moderate or Severe Proteinuria: A Systematic Review and Network Meta-Analysis

Abstract

Objective. Numerous studies have demonstrated that the efficacy of drugs differs in idiopathic membranous nephropathy (IMN) patients with moderate or high proteinuria. However, there is no systematic comparison confirming it. This network meta-analysis (NMA) was performed to respectively compare the efficacy of ten IMN treatments in patients with moderate and high proteinuria and compare the risk of adverse events with 10 IMN regimens. Methods. Randomized controlled trials (RCTs) and observational studies analyzing the main therapeutic regimens for IMN were included from some databases. Network comparisons were performed to analyze the rates of total remission (TR), bone marrow suppression, and gastrointestinal symptoms. The surface under the cumulative ranking area (SUCRA) was calculated to rank interventions. Results. Seventeen RCTs and eight observational studies involving 1778 patients were pooled for comparison of ten interventions. Steroid + tacrolimus (TAC) showed the highest probabilities of TR whether patients had severe proteinuria or not (SUCRA 89.5% and 88.9%, separately). Rituximab (RTX) was more beneficial for TR on patients with proteinuria <8 g/d (SUCRA 66.0%) and was associated with a lower risk of bone marrow suppression and gastrointestinal symptoms (SUCRA 21.7% and 21.4%, separately). TAC + RTX and steroids + cyclophosphamide induced the highest rates of bone marrow suppression (SUCRA 90.6% and 88.3%, separately) and gastrointestinal symptoms (SUCRA 86.0% and 72.1%, separately). Conclusions. Steroids + TAC showed significant efficacy in patients with all degrees of proteinuria, while RTX was more effective in patients with moderate proteinuria and was safer in bone marrow suppression and gastrointestinal symptoms.

Phospholipase A2 Receptor Antibodies and Clinical Prognosis in Patients with Idiopathic Membranous Nephropathy: An Updated Systematic Review and Meta-Analysis

“…The optimal immunosuppressive regimen for IMN remains controversial. The effect of tacrolimus [43] and cyclosporine A [44] on remission was relatively better than that of cyclophosphamide, rituximab, and mycophenolate mofetil. Although rituximab was superior in the decline of proteinuria and PLA2R-ab [45], the result was not consistent, and more randomized trials are needed.…”

Cyclophosphamide induced early remission and was superior to rituximab in idiopathic membranous nephropathy patients with high anti-PLA2R antibody levels

“…The recently published network meta-analysis partly overcame this limitation. There have been six network meta-analyses in the treatment of IMN, but none of them found significant differences of remission between RTX and CYC (Table 3) [26][27][28][29][30][31]. The network meta-analysis by Zheng et al in 2019 covered 13 immunosuppressive agents in IMN and found that TAC and CYC are superior to other immunosuppressive agents including RTX in terms of total remissions but with no statistical significance [29].…”

“…The network meta-analysis by Bose et al in 2022 found that CYC had nonsignificant effects on inducing CR compared with RTX (OR 0.35, CI 0.10-1.24) [31]. Another network meta-analysis by Chen et al in 2022 showed that RTX and steroid + CYC both were better treatments than others for total remissions in patients with proteinuria < 8 g/d [30]. Compared with the above studies, our direct meta-analysis included more studies and came to novel findings on the efficacy in different follow-up periods and antiPLA2Rab levels.…”

Implications of rituximab pharmacokinetic and pharmacodynamic alterations in various immune-mediated glomerulopathies and potential anti-CD20 therapy alternatives

“…Nevertheless, no statistically significant correlation between the PU level and RTX levels was attained in this, admittedly, rather small study (n=20) (82). Chen et al in their meta-analysis of studies that described the treatment of MN also proved that reduced proteinuria is associated with a better treatment response to RTX (84).…”

“…Chen et al. in their meta-analysis of studies that described the treatment of MN also proved that reduced proteinuria is associated with a better treatment response to RTX ( 84 ).…”