Effectiveness and safety of rituximab monotherapy versus conventional regimens for adult idiopathic membranous nephropathy: real-world retrospective study

Background The 2021 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend immunotherapeutic regimens for idiopathic membranous nephropathy (IMN), including glucocorticoids (GC) with cyclophosphamide (CYC) or calcineurin inhibitors (CNIs), as well as biologics. However, the comparative effectiveness remains insufficiently explored. This study aimed to evaluate the effectiveness and safety of rituximab (RTX) versus conventional regimens. Methods This study retrospectively included 310 IMN patients diagnosed with nephrotic syndrome (NS), who were divided into three groups: RTX group (n=62), glucocorticoid with cyclophosphamide (GC+CYC) group (n=124), and glucocorticoid with calcineurin inhibitor (GC+CNI) group (n=124). Treatment effectiveness and safety were assessed at the 12 months. The primary endpoint was clinical remission at 12 months. Secondary endpoints, included clinical remission rate, relapse rate, and safety and occurrence of adverse events(AEs)at 24 months. Results At 12 months, 44/62 (71.0%) achieved clinical remission, with 18 (29.0%) achieving CR in the rituximab group,. In the GC+CYC group, 90/124 (72.6%) achieved clinical remission, 48 (38.7%) achieving CR. In the GC+CNI group, 97/124 (78.2%) achieved clinical remission, with 52 (41.9%) achieving CR. At 24 months, 33/35 (94.3%) achieved clinical remission, with 18 (51.4%) achieving CR in the RTX group. In the GC+CYC group, 102/115 (88.7%) achieved clinical remission, with 44 (38.3%) achieving CR. In the GC+CNI group, 98/114(86.0%) achieved clinical remission, with 47 (41.2%) achieving CR. The clinical and complete remission rates were significantly higher in the rituximab group than in the conventional treatment groups (clinical remission: 94.3% vs. 88.7% vs. 86.0%, P = 0.002; CR: 51.4% vs. 38.3% vs. 41.2%, P = 0.000). Logistic regression analysis revealed anti-phospholipase A2 receptor (PLA2R) antibody titer (OR = 0.998, P = 0.016) was identified as an independent risk factor for non-remission. The RTX group showed lower rates of overall AEs (27.4%), none of the AEs were severe. Conclusion Rituximab demonstrated non-inferior clinical remission rates at 12 months compared to CYC and CNIs. Rituximab was also associated with lower relapse rates and better safety profile. These findings suggest that rituximab offers distinct advantages in maintaining long-term clinical remission and may be considered an effective treatment regimen for IMN patients at risk of disease progression.