A comparative study on the efficacy of rituximab combined with tacrolimus and methylprednisolone in the treatment of patients with moderate-high risk idiopathic membranous nephropathy.

OBJECTIVE: To compare the efficacy of combining methylprednisolone with either rituximab or tacrolimus for treating idiopathic membranous nephropathy (IMN). METHOD: This research is designed as a prospective study (TCTR20260515001, URL: https://www.thaiclinicaltrials.org/show/TCTR20260515001). A total of 210 IMN patients treated at Binzhou People's Hospital from October 2021 to October 2024 were enrolled and randomly assigned to one of three groups: a control group, intervention group 1, and intervention group 2. The control group received methylprednisolone alone. Intervention group 1 underwent the same methylprednisolone therapy plus intravenous rituximab, while intervention group 2 received methylprednisolone combined with oral tacrolimus. General data, clinical efficacy after treatment, phospholipase A2 receptor (PLA2R), renal function indicators, inflammatory indicators, urinary immune indicators, quality of life, and adverse reactions were compared. Multivariate logistic regression analysis was used to examine whether the treatment regimen was an independent influencing factor for the patient's therapeutic effect. Subgroup analysis was used to compare the efficacy differences among patients with different characteristics after receiving different treatment plans. RESULTS: The total effective rate of treatment in intervention group 1 was higher than that in intervention group 2 and the control group (P<0.05). With increasing treatment time, PLA2R, 24-hour urine protein quantification, serum creatinine (SCr), blood urea nitrogen (BUN), inflammatory indicators, and urinary immune indicators of all patients declined, and intervention group 1 exhibited lower values than both intervention group 2 and the control group (P<0.05); while plasma albumin (ALB) and Short Form-36 Health Survey score (SF-36) gradually increased with treatment time, and intervention group 1 exhibited higher values than intervention group 2 and the control group (P<0.05). However, no discernible statistical difference was observed in the total incidence of adverse reactions among the three groups (P>0.05). Multivariate logistic regression analysis showed that after adjusting for confounding factors, the rituximab combination regimen was an independent influencing factor for better therapeutic effects in patients with moderate to high-risk idiopathic membranous nephropathy (P<0.05). The results of the subgroup analysis showed that the therapeutic advantages of rituximab combined with methylprednisolone remained consistent across patients with different clinical characteristics. CONCLUSION: After adjusting for confounding factors such as age, diabetes, and baseline renal function, concurrent rituximab and methylprednisolone showed a more favorable therapeutic outcome compared to the tacrolimus regimen, and it was applicable to a wider range of patients.