Low-Dose Rituximab vs. Modified Ponticelli Regimen in the Treatment of Primary Membranous Nephropathy – A Randomized Controlled Trial

Background The modified Ponticelli regimen (mPR) with cyclical steroids and cyclophosphamide is first-line therapy for primary membranous nephropathy (PMN). While low-dose rituximab (RTX) has been effective in inducing remission in PMN, there is a paucity of head-to-head trials comparing it with the first-line regimen. This pilot study aimed to assess the feasibility, safety, and efficacy of low-dose RTX compared with Mpr in PMN. Materials and Methods In this single-center study, 68 patients with PMN and nephrotic syndrome were randomly assigned to receive either two doses of RTX (500 mg) given 15 days apart or mPR. Results 15/34 patients (44.12%) in the RTX group and 17/34 patients (50%) in the mPR group had achieved the primary outcome of partial or complete remission at 6 months (Risk difference RD -5.88%, 95% confidence interval CI = -29.57 to 17.80%, p = 0.578). At 12 months, remission rate was 59.27% in the RTX arm and 69.57% in the mPR arm (Risk difference -10.31%, 95% CI = -36.71 to 16.09%, p = 0.444). Adverse events (P = 0.007), including leukopenia, infections, and hyperglycemia, were significantly more frequent in the mPR arm. CD19 + ve B-cells were suppressed by 1 month in all patients at this rituximab dose, but 64% had recovery by 6 months. Conclusion This pilot study suggested that low-dose RTX could achieve sufficient B-cell suppression and short-term remission rates comparable to mPR with fewer adverse events. It demonstrates the feasibility and safety of low-dose RTX in PMN. Further studies with larger cohorts are required to confirm these findings.