Low-Dose Rituximab in the Treatment of Primary Membranous Nephropathy - A Systematic Review and Meta-Analysis

Introduction. Rituximab (RTX) holds promise as a treatment for idiopathic membranous nephropathy (IMN). While effective in standard regimens, the application of RTX is hampered by cost burdens and severe side effects. To address these issues, low-dose RTX has been proposed as an intervention strategy. Yet, the efficacy of this approach in treating IMN remain subject of debate. This systematic review and meta-analysis seek to examine the effectiveness of low-dose RTX in adult patients with IMN. Methodology. A literature search was conducted using PubMed, Wiley Online Library, ScienceDirect, Cochrane Library, Springer and other sources, published between 2004 and 2024. Specifically, articles reporting the intravenous application of RTX at doses lower than four weekly infusions of 375 mg/m² or two infusions of 1 gram each on day 0 and day 15 were considered for inclusion. The primary outcomes were complete response (CR) and partial response (PR) rates at last follow-up. Secondary endpoints included serum creatinine levels, serum albumin levels, 24-hour proteinuria levels, protein-creatinine ratio (PCR), estimated glomerular filtration rate (eGFR) and anti-PLA2R antibody levels. Results. Sixteen articles were included in this meta-analysis. The pooled analysis of odds ratios (OR) revealed that both main-line (OR = 0.48, 95% CI = 0.30-0.75, p = 0.001) and second-line (OR = 0.27, 95% CI = 0.11-0.67, p = 0.005) RTX treatments induced complete remission (CR) in IMN patients. At the last follow-up, patients treated with both main-line (mean difference [MD] = 1.45, 95% CI = 1.00-1.91, p < 0.00001) and second-line (MD = 0.88, 95% CI = 0.23-1.53, p < 0.00001) RTX treatments showed a significant increase in serum albumin levels. Conversely, in the analysed second line RTX therapy patients, low eGFR trend was noted in the post treatment arm compared to baseline levels (MD = 10.57, 95% CI = 0.30-20.83, p = 0.04). Moreover, RTX was found to be effective in reducing PCR (MD = 24.10, 95% CI= 1.07 to 47.13, p = 0.04) and depleting PLA2R antibody levels (MD = 127.36, 95% CI = 14.90-239.81, P = 0.03). However, RTX might be less effective in lowering proteinuria and serum creatinine levels in patients with nephrotic syndrome. Conclusion. Rituximab in a low-dose regimen is quite effective in treating adult patients with IMN. Therefore, it can be considered a promising treatment for both main-line and rescue therapy. More randomized controlled trials and research on optimizing the low-dose regimen, based on various health factors, are warranted.