Comparison of the efficacy of rituximab monotherapy and combined immunotherapy for primary membranous nephropathy: a real-world cohort study

Background Rituximab (RTX) has been established as a first-line treatment for primary membranous nephropathy (pMN). However, the efficacy difference between RTX monotherapy and combined regimens incorporating additional immunosuppressants (e.g., glucocorticoids or calcineurin inhibitors) remains unclear, particularly in patient subgroups with distinct clinical and immunological characteristics. Therefore, clarification of individualized treatment strategies is urgently needed. Methods A total of 98 pMN patients receiving RTX-based treatment were enrolled and divided into three groups: monotherapy (RTX), doublet therapy (RTX in combination with tacrolimus), and triplet therapy (RTX, tacrolimus, and glucocorticoids concurrently). We compared the 12-month total remission rate, changes in renal function, proteinuria levels, and B cell depletion across groups, with subgroup analyses stratified by age and anti-PLA2R antibody titer. Results The monotherapy group achieved a significantly higher total remission rate than the doublet and triplet therapy groups. Despite poorer baseline renal function in the combined treatment groups, their improvements in renal function and proteinuria reduction at 12 months were inferior to those of the monotherapy group. Subgroup analyses revealed that monotherapy advantages were particularly prominent in patients with anti-PLA2R antibody titer ≤ 200 RU/mL and those aged > 60 years. Additionally, the monotherapy group exhibited unique kinetic characteristics of B cell depletion. Conclusion This real-world study demonstrates that RTX monotherapy provides superior clinical remission and renal protection compared to combined regimens, challenging the necessity of routine combined immunosuppressive treatment. The significant benefits observed in elderly patients and those with low anti-PLA2R antibody titers support RTX monotherapy as the preferred initial treatment strategy for most pMN patients.