基于倾向性评分匹配法评价仿制药沙丁胺醇雾化液治疗儿童急性喘息的有效性和安全性的非随机对照试验  

Effectiveness and safety of generic nebulized salbutamol for acute wheezing in children: A study based on propensity score matching

作　　者：陈镜龙 陆泳 冯海燕 钱莉玲 王立波 陆爱珍 CHEN Jing-long;LU Yong;FENG Hai-yan;QIAN Li-ling;WANG Li-bo;LU Ai-zhen(Respiratory Department,Children’s Hospital of Fudan University,Shanghai 201102,China)

机构地区：[1]复旦大学附属儿科医院呼吸科,上海201102

出　　处：《中国循证儿科杂志》2020年第4期285-288,共4页Chinese Journal of Evidence Based Pediatrics

基　　金：上海市科委西医引导项目:17411960700。

摘　　要：目的探讨仿制药沙丁胺醇雾化液治疗儿童急性喘息的有效性和安全性。方法非随机对照试验。针对临床确诊存在急性喘息发作的、年龄<18岁的、门诊临床实际处方,分为原研药组(GSK公司生产,规格为5 mg·(2 mL)^-1沙丁胺醇雾化吸入溶液)和仿制药组(上海信谊金朱药业有限公司生产,规格为2.5 mg·(2.5 mL)^-1硫酸沙丁胺醇雾化吸入溶液),均按以下剂量和方式给药:①体重≤20 kg者每次2.5 mg,体重>20 kg者每次5.0 mg;②配伍生理盐水或其他雾化药物(按临床实际需要)至4 mL雾化液,氧流量6~8 L·min^-1驱动下或空气压缩泵雾化吸入,每天2次,疗程3 d。以家长日记卡方式收集用药3 d的主要结局指标[每日第1次雾化前后临床症状严重度(CS)评分差值(ΔCS)]和次要结局指标(心律失常、肌肉震颤和腹泻等不良反应)。结果2018年2月至2019年6月在复旦大学附属儿科医院呼吸科门诊因急性喘息发作的841例患儿,原研药组438例,仿制药组403例,2组差异有统计学意义的基线项目(性别、年龄、主要诊断、雾化用药配伍、合并全身用药)作为协变量行1∶1倾向性评分匹配,2组各有299例急性喘息发作患儿达到了设定匹配容差为0.1。第1~3 d每日第1次ΔCS原研药组[(-0.38±0.48)vs(-0.43±0.49)vs(-0.58±0.49)]和仿制药组[(-0.47±0.50)vs(-0.50±0.50)vs(-0.59±0.49)]均随时间呈下降趋势,2组组内3 dΔCS差异均有统计学意义,第3 dΔCS均显著低于第1和2 d。2组患儿第1 dΔCS差异有统计学意义,第2和3 dΔCS差异均无统计学意义。急性喘息发作的841例患儿中,无因严重不良反应退出观察的病例。原研药组和仿制药组肌肉震颤发生率分别为2.5%(11/438)和4.5%(18/403),腹泻发生率分别为0.7%(3/438)和1.5%(6/403),差异均无统计学意义。结论沙丁胺醇雾化吸入液缓解儿童急性喘息发作疗效仿制药不低于原研药,安全性相似。Objective:To evaluate the effectiveness and safety of generic nebulized salbutamol in children with acute wheezing.Methods:This was a non-randomized controlled trial.Patients younger than 18 years old with acute wheezing episodes were divided into the original drug group[5 mg·(2 mL)^-1 albuterol inhalation solution,produced by GSK company]and the generic drug group[2.5 mg·(2.5 mL)-1 albuterol sulfate nebulized inhalation solution,produced by Shanghai Xinyi Jinzhu Pharmaceutical Co.,Ltd.]according to the actual clinical prescriptions.The dose and administration were the following:a.2.5 mg each time for those with weight≤20 kg or 5.0 mg each time for those with weight>20 kg;b.compatible with normal saline or other nebulized drugs(according to actual clinical needs)to 4 mL liquid,driven by oxygen flow 6 to 8 L·min^-1 or air compression pump,twice a day for 3 days.Each participant recorded a log every day.The primary outcome was the difference in clinical symptom severity(ΔCS)each day,and the secondary outcome was the adverse event such as arrhythmia,muscle tremor or diarrhea.Results:A total of 841 outpatients consulting in Children’s Hospital of Fudan University from February 2018 to June 2019 with acute wheezing were included,438 cases in the original group and 403 cases in the generic group.All patients completed the follow-up period.The baseline items(gender,age,main diagnosis,compatibility of nebulized medications and combined systemic medication)with statistically significant differences between the two groups were treated as a covariate of the propensity score.According to 1∶1 matching and the matching tolerance set as 0.1,there were 299 cases left in each group.ΔCS each day in both groups decreased over time[(-0.38±0.48)vs(-0.43±0.49)vs(-0.58±0.49)for 3 days in the original group,(-0.47±0.50)vs(-0.50±0.50)vs(-0.59±0.49)for 3 days in generic group].There were statistically significant differences inΔCS among 3 days in both groups.TheΔCS on day 3 was significantly lower than that on day 1 and

关 键 词：沙丁胺醇 喘息 仿制药 倾向性评分匹配 

分 类 号：R725.6[医药卫生—儿科]