Combination of Rituximab, Low-Dose Cyclophosphamide, and Prednisone for Primary Membranous Nephropathy: A Case Series With Extended Follow Up

医学 美罗华 强的松 环磷酰胺 四分位间距 内科学 胃肠病学 膜性肾病 单中心 肌酐 外科 泌尿科 肾小球肾炎 化疗 淋巴瘤
作者
Reza Zonozi,Karen Laliberte,Noah Huizenga,Jillian K. Rosenthal,Anushya Jeyabalan,A. Bernard Collins,Frank B. Cortazar,John L. Niles
出处
期刊:American Journal of Kidney Diseases [Elsevier BV]
卷期号:78 (6): 793-803 被引量:39
标识
DOI:10.1053/j.ajkd.2021.04.014
摘要

B-cell depletion with rituximab has emerged as a first-line therapy for primary membranous nephropathy (MN). However, most patients do not achieve complete remission with rituximab monotherapy. In this case series, we report longer-term remission and relapse rates, anti-phospholipase A2 receptor (PLA2R) antibody levels, B-cell levels, and serious adverse events in patients with primary MN who received rituximab combined with an initial short course of low-dose oral cyclophosphamide and a course of rapidly tapered prednisone.Single-center retrospective case series.60 consecutive patients with primary MN treated with the combination of rituximab, low-dose cyclophosphamide, and prednisone at the Vasculitis and Glomerulonephritis Center at the Massachusetts General Hospital.After treatment initiation, median follow-up was 38 (interquartile range [IQR], 25-62) months; 100% of patients achieved partial remission, defined as a urinary protein-creatinine ratio (UPCR) < 3 g/g and a 50% reduction from baseline, at a median of 3.4 months. By 2 years after treatment initiation, 83% achieved complete remission, defined as a UPCR < 0.3 g/g. The median time to complete remission was 12.4 months. Immunologic remission (defined by an anti-PLA2R titer < 14 RU/mL) was achieved by 86% and 100% of anti-PLA2R seropositive patients (n = 29) at 3 and 6 months, respectively, after treatment initiation. After 1 year, the median UPCR fell from 8.4 (IQR, 5.0-10.7) to 0.3 (IQR, 0.2-0.8) g/g (P < 0.001). No patient relapsed throughout the duration of B-cell depletion. Relapse occurred in 10% of patients at 2 years after the onset of B-cell reconstitution following the last rituximab dose. Over a combined follow-up time of 228 patient-years, 18 serious adverse events occurred. One death occurred unrelated to treatment or primary MN, and 1 patient progressed to kidney failure requiring kidney replacement therapy.Absence of a comparison group.All patients with primary MN treated with combination therapy achieved partial remission and most achieved a durable complete remission with an acceptable safety profile.
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