摘要
目的评价小剂量利妥昔单抗联合糖皮质激素治疗儿童狼疮性肾炎的临床疗效,观察不良反应。方法选取本院2014年1月至2017年1月期间确诊的儿童狼疮性肾炎42例,在口服醋酸泼尼松基础上,联合应用利妥昔单抗,每周1次,100 mg/次,共4～6次。于第0.5、1、3、6、12个月末评估系统性红斑狼疮疾病活动指数(systemic lupus erythematosus disease activity index 2000, SLEDAI-2K)、红细胞沉降率、补体C3、C4、24小时尿蛋白定量、CD20细胞计数等指标。比较利妥昔单抗使用前后糖皮质激素使用情况,观察利妥昔单抗治疗后不良反应。结果在第2周末时SLEDAI-2K降至(13.7±4.1)分,与治疗前(17.4±4.8)分相比差异有统计学意义(t=2.677,P=0.032),在第3个月末时SLEDAI-2K下降至最低水平(4.1±1.1)分,同时观察到治疗后各个时点红细胞沉降率(P=6.068,P=0.033)、补体C3 (F=10.543, P=0.009)和C4 (F=9.478,P=0.011)显著性改善,并维持至第12个月末;24小时尿蛋白定量在第4周末时降至(15.3±5.0) mg/kg,与治疗前(32.4±7.2)mg/kg相比差异有统计学意义(t=2.677,P=0.032),第3个月末时降至正常范围内(4.8±1.4) mg/kg,并在第12个月末仍维持低水平蛋白尿(5.2±1.7) mg/kg;外周血B细胞计数(CD20细胞)在第2周末时降至(27.94±4.24)个/μl,与治疗前(66.45±7.46)个/μl相比差异有统计学意义(t=2.745, P=0.023),在此后6个月内均维持B细胞耗竭状态,在第12个月末时明显回升至(24.66±5.57)个/μl,与治疗前相比差异仍具有统计学意义(P<0.05);在第3个月末和第6个月末时,醋酸泼尼松的中位剂量分别是10 (5,15) mg (Z=-2.972,P=0.016)和7.5 (5,12.5)mg (Z=-3.145,P=0.007),均较治疗前20.25 (10,50)mg显著下降,48%(20/42)患儿在第6个月末时醋酸泼尼松维持剂量不超过5 mg;观察到7例共12人次利妥昔单抗输注相关反应综合征,12人次的泌尿系感染,3人次肺炎,14人次上呼吸道感染,未影响利妥昔单抗全程应用。结论小剂量利妥昔单抗联合糖皮质激素治疗儿童狼疮性肾炎疗效确切,能较快实现糖皮质激素小剂量维持,且不良反应较少,可作为临床一线选择。
Objective To assess the clinical efficacy and safety of low-dose rituximab combined with glucocorticoid in children with lupus nephritis. Methods Forty-two children with lupus nephritis from January 2014 to January 2017 were treated with rituximab on the basis of oral prednisone at 100 mg/time, 1 time per week for 4-6 weeks. At the end of 0.5, 1, 3, 6 and 12 months, SLEDAI-2K, ESR, complement C3, C4, 24-hour urinary protein quantification and CD20 cell count were observed. The dose of glucocorticoid before and after rituximab treatment was compared and the side effect of rituximab treatment was observed. Results At the end of the 2nd week, SLEDAI-2K reached (13.7±4.1), which was significantly different from that before treatment (17.4±4.8)(t=2.677, P=0.0320). At the end of 3rd month, SLEDAI- 2K decreased to the lowest level (4.1±1.1). Erythrocyte sedimentation rate (F=6.068, P=0.033), C3 (F=10.543, P = 0.009) and C4 (F= 9.478, P = 0.011) at each time point after treatment were also significantly improved and maintained until the end of 12th month. At the end of the 4th week, 24- hour urinary protein content decreased to (15.3±5.0) mg/kg, which was significantly different from that before treatment (32.4±7.2) mg/kg (t=2.677, P=0.032). At the end of the 3rd month, 24-hour urinary protein content decreased to (4.8±1.4) mg/kg in the normal range, and maintained a low level of proteinuria (5.2±1.7) mg/kg at the end of the 12th month. At the end of the 2nd week, the CD20 cells count decreased to (27.94±4.24)/μl, which was significantly different from that before treatment (66.45±7.46)/μl (t=2.745, P=0.023). Within the following six months, the exhaustion of B cells was maintained. At the end of 12th month, the cell count increased to (24.66±5.57)/μl, which was significantly lower than that before treatment. At the end of the 3rd month and the end of the 6th month, the median doses of prednisone were 10(5,15) mg (Z= 2.972, P = 0.016) and 7.5(5, 12.5) mg (Z=3.145, P=0.007), which were significantly lower than those before treatment 20.25(10, 50)mg. The dose of prednisone in 48%(20/42) children was less than 5 mg at the end of the 6th month. Twelve cases of rituximab infusion-related response syndromes, 12 cases of urinary tract infections, 3 cases of pneumonia and 14 cases of upper respiratory tract infections were observed without affecting the whole course of rituximab administration. Conclusion Low-dose rituximab combined with glucocorticoid is effective in the treatment of lupus nephritis in children, and it has less adverse reactions. Therefore, it can be used as the first-line clinical treatment.
作者
陈捷
CHEN Jie(Department of Pediatrics, Fujian Provincial Hospital, Fuzhou 350001, China;Provincial Clinical College, Fujian Medical University, Fuzhou 350001, China)
出处
《创伤与急诊电子杂志》
2018年第4期223-227,共5页
Journal of Trauma and Emergency(Electronic Version)
