目的 探討利妥昔單抗聯(lián)合環(huán)磷酰胺對特發(fā)性膜性腎?。↖MN）患者的臨床療效。方法 選取2018年8月—2020年8月石家莊市人民醫(yī)院129例IMN患者作為研究對象，根據(jù)納入患者的治療方案將患者分為環(huán)磷酰胺組、利妥昔單抗組和利妥昔單抗與環(huán)磷酰胺聯(lián)用組（簡稱聯(lián)用組），環(huán)磷酰胺組予以注射用環(huán)磷酰胺治療，靜脈滴注，每次0.8～1.0 g，每月1次；治療6個月后達到臨床完全緩解或部分緩解，繼續(xù)治療3個月（累積劑量＜10 g），治療6個月無效者停用。利妥昔單抗組予以利妥昔單抗注射液，靜脈滴注，375 mg·m^-2，每周1次。聯(lián)用組予以利妥昔單抗注射液及注射用環(huán)磷酰胺治療，用法用量分別同單用組。3組均持續(xù)治療6個月。比較3組疾病緩解率、IMN相關(guān)指標［24 h尿蛋白定量、抗磷脂酶A2受體（PLA2R）抗體、血肌酐］、T淋巴細胞亞群分布、尿中攻膜復(fù)合物（C5b-9）、免疫球蛋白G4（IgG4）、復(fù)發(fā)率及感染并發(fā)癥發(fā)生率。結(jié)果 聯(lián)用組總有效率（81.40%）較環(huán)磷酰胺組、利妥昔單抗組（53.49%、60.47%）顯著升高（P＜0.05）。治療后，3組24 h尿蛋白定量、抗PLA2R抗體、尿C5b-9、IgG4水平均較本組治療前顯著下降（P＜0.05）；且治療后聯(lián)用組24 h尿蛋白定量、抗PLA2R抗體、尿C5b-9、IgG4水平較環(huán)磷酰胺組、利妥昔單抗組顯著降低（P＜0.05）。治療后，3組CD4⁺、CD4⁺/CD8⁺均較本組治療前顯著下降（P＜0.05），CD8⁺顯著升高（P＜0.05），且治療后聯(lián)用組CD4⁺、CD4⁺/CD8⁺較環(huán)磷酰胺組、利妥昔單抗組顯著降低（P＜0.05），CD8⁺較環(huán)磷酰胺組、利妥昔單抗組顯著升高（P＜0.05）。聯(lián)用組12個月復(fù)發(fā)率（2.33%）較環(huán)磷酰胺組、利妥昔單抗組（20.93%、18.60%）顯著降低（P＜0.05）；3組感染并發(fā)癥比較，差異無統(tǒng)計學(xué)意義（P＞0.05）。結(jié)論 利妥昔單抗聯(lián)合環(huán)磷酰胺可有效緩解IMN病情，并改善患者腎功能、免疫功能，且安全可靠。

Objective To investigate the clinical efficacy of rituximab in combination with cyclophosphamide in treatmeng of patients with idiopathic membranous nephropathy (IMN). Methods 129 patients with IMN in Shijiazhuang People's Hospital from August 2018 to August 2020 were selected as study subjects. According to the treatment plan of the included patients, they were divided into a cyclophosphamide group, a rituximab group, and a combination of rituximab and cyclophosphamide group (referred to as the combination group). The cyclophosphamide group was treated with Cyclophosphamide Injection, intravenous drip, 0.8— 1.0 g each time, once a month. After six months of treatment, complete or partial clinical remission was achieved. Treatment continued for three months (cumulative dose < 10 g), and those who failed after six months were discontinued. The rituximab group received Rituximab Injection, intravenous drip, 375 mg·m^-2, once a week. The combination group was treated with Rituximab Injection and Cyclophosphamide Injection, with the same usage and dosage as the single use group. All three groups were treated continuously for six months. The remission rate, nephropathy-related indicators [24 h urine protein quantification, phospholipase A2 receptor antibody (PLA2R), blood creatinine], T lymphocyte subsets, urinary tapping membrane complex (C5b-9), immunoglobulin G4 (IgG4), relapse rate and complication rate of infection were also compared among the three groups. Results The disease remission rate was higher in the combination group (81.40%) compared with cyclophosphamide group and rituximab group (53.49%, 60.47%) (P < 0.05). After treatment, the 24 h urinary protein quantification, anti PLA2R antibody, urinary C5b-9, and IgG4 levels in three groups significantly decreased before treatment of same group (P < 0.05), 24 h urine protein quantification, PLA2R, urine C5b-9 and IgG4 were lower in the combination group compared with cyclophosphamide group and rituximab group after treatment (P < 0.05). After treatment, the CD4⁺and CD4⁺/CD8⁺ levels in three groups significantly decreased compared to before treatment of same group (P < 0.05), while the CD8⁺ levels significantly increased (P < 0.05). CD4⁺, CD4⁺/CD8⁺ were lower in the combination group compared with cyclophosphamide group and rituximab group after treatment, and CD8⁺ was higher in the combination group compared with cyclophosphamide group and rituximab group (P < 0.05). The 12-month recurrence rate was lower in the combination group (2.33%) compared with cyclophosphamide group and rituximab group (20.93% and 18.60%) (P < 0.05). The differences were not statistically significant when comparing the complications of infection in the three groups (P > 0.05). Conclusion Rituximab combined with immunosuppressants-cyclophosphamide can effectively alleviate IMN disease and improve renal and immune function, and the treatment is safe and reliable.

R983

河北省2023年度醫(yī)學(xué)科學(xué)研究課題計劃項目（20231601）