INTRODUCTION: Rituximab, Rtx is a promising therapeutic agent in treating idiopathic membranous nephropathy, IMN. In most studies, Rtx was used alone with RAS inhibitors and the time to partial remission were 4 to 7 months. This is a single center perspective study to evaluate the efficacy and safety of Rtx combined with modified immunosuppression regimens in treating Chinese IMN patients with persistent nephrotic syndrome.
METHODS: The proposed regimen are two doses of 1000mg Rtx given intravenously, separated by 2 weeks. Second dose will only be given to the patients who had CD19+ B lymphocytes > 5/mm3 after the first dose. If proteinuria improved significantly, 1000mg Rtx will be repeated every 6 months for 2 years. Concurrent immunosuppression regimens are modified. Complete remission, CR was defined as albumin>35g/L, proteinuria< 0.3g/d. Partial remission, PR was defined as proteinuria improved > 50% of the baseline level.
RESULTS: From 2017.12 to 2018.10, 16 IMN patients (M: F 11:5, mean age 40.1±12.1 years, 11 had prior immunosuppression therapy) received Rtx treatment (1 dose in 13 patients and 2 doses in 3 patients), all of whom achieved B cell depletion. Their baseline proteinuria, ALB, serum creatine and anti-PLA2R antibody titers were 11.41±6.42g/d, 22.7±4.8g/L, 0.98±0.32mg/dL and 84.0 EU/ml (IQR 24.6-125.7) (n=12). The concurrent immunosuppression regimens were listed in Table 1. 12/12 patients showed negative anti-PLA2R results in 2.0 months (IQR 1.5-4.9). Among the 14 patients who had been followed > 6 months, proteinuria improved from 11.86±6.69g/d to 3.34±3.74g/d (P<0.001) and albumin improved from 23.1±5.0g/L to 37.4±6.4g/L (P<0.001). One patient achieved CR, 12 patients achieved PR and 1 patient showed improving proteinuria > 30%. The median time to PR was 2.0 months (IQR 2.0-5.5) after Rtx treatment. The median time to B cell relapse were 6.0 months (IQR 5.25-6.0) and 7/12 patients received 1g Rtx redosing at the 6th month. Infusion reactions such as rash and itching were seen in 8 patients and only 1 patient showed skin infection.
CONCLUSIONS: Conclusion: Rituximab combined with modified immunosuppression regimens showed promising treatment response and relatively safe profile in persistent nephrotic Chinese IMN patients.
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