加拿大麦克马斯特大学Reed AC Siemieniuk团队对covid-19的药物治疗进行了生活系统回顾和网络荟萃分析。该成果发表在2020年7月30日出版的《英国医学杂志》上。
为了比较covid-19的治疗效果，研究组在美国疾病预防控制中心COVID-19研究文章可下载数据库，包括25个电子数据库和6个附加中文数据库中检索截至2020年7月20日的文献，筛选出将疑似、可能或确诊covid-19的参与者随机分配至药物治疗、标准治疗或安慰剂的随机临床试验，进行生活系统回顾和网络荟萃分析。
2020年6月26日进行的分析中包括23项随机试验。由于存在偏倚（缺乏盲法）和严重的不精确性，大多数比较证据的确定性非常低。与标准治疗相比，糖皮质激素是唯一可以减少死亡率（每千名患者减少37例）和机械通气率（每千名患者减少31例）的干预措施（中确定性）。这些估计基于直接证据；由于网络异质性，糖皮质激素的网络估计与标准治疗相比不那么精确。
与标准治疗相比，三种药物可能会减少症状持续时间：其中羟氯喹平均减少4.5天，低确定性；瑞德西韦平均减少2.6天，中确定性；洛匹那韦-利托那韦平均减少1.2天，低确定性。与其他干预措施相比，羟氯喹可能会增加不良事件的风险，而瑞德西韦可能不会显著增加导致停药的不良反应的风险。其他干预措施没有足够的患者来有意义地解释导致药物停用的不良反应。
总之，与标准治疗相比，糖皮质激素可能会降低covid-19患者的死亡率和机械通气率。由于大多数随机对照试验规模很小，并且存在研究局限性，因此大多数干预措施的有效性尚不确定。
附：英文原文
Title: Drug treatments for covid-19: living systematic review and network meta-analysis
Author: Reed AC Siemieniuk, Jessica J Bartoszko, Long Ge, Dena Zeraatkar, Ariel Izcovich, Hector Pardo-Hernandez, Bram Rochwerg, Francois Lamontagne, Mi Ah Han, Elena Kum, Qin Liu, Arnav Agarwal, Thomas Agoritsas, Paul Alexander, Derek K Chu, Rachel Couban, Andrea Darzi, Tahira Devji, Bo Fang, Carmen Fang, Signe Agnes Flottorp, Farid Foroutan, Diane Heels-Ansdell, Kimia Honarmand, Liangying Hou, Xiaorong Hou, Quazi Ibrahim, Mark Loeb, Maura Marcucci, Shelley L McLeod, Sharhzad Motaghi, Srinivas Murthy, Reem A Mustafa, John D Neary, Anila Qasim, Gabriel Rada, Irbaz Bin Riaz, Behnam Sadeghirad, Nigar Sekercioglu, Lulu Sheng, Charlotte Switzer, Britta Tendal, Lehana Thabane, George Tomlinson, Tari Turner, Per O Vandvik, Robin WM Vernooij, Andrés Viteri-García, Ying Wang, Liang Yao, Zhikang Ye, Gordon H Guyatt, Romina Brignardello-Petersen
Issue&Volume: 2020/07/30
Abstract: Objective To compare the effects of treatments for coronavirus disease 2019 (covid-19).
Design Living systematic review and network meta-analysis.
Data sources US Centers for Disease Control and Prevention COVID-19 Research Articles Downloadable Database, which includes 25 electronic databases and six additional Chinese databases to 20 July 2020.
Study selection Randomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles.
Methods After duplicate data abstraction, a bayesian random effects network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance.
Results 23 randomised controlled trials were included in the analysis performed on 26 June 2020. The certainty of the evidence for most comparisons was very low because of risk of bias (lack of blinding) and serious imprecision. Glucocorticoids were the only intervention with evidence for a reduction in death compared with standard care (risk difference 37 fewer per 1000 patients, 95% credible interval 63 fewer to 11 fewer, moderate certainty) and mechanical ventilation (31 fewer per 1000 patients, 47 fewer to 9 fewer, moderate certainty). These estimates are based on direct evidence; network estimates for glucocorticoids compared with standard care were less precise because of network heterogeneity. Three drugs might reduce symptom duration compared with standard care: hydroxychloroquine (mean difference 4.5 days, low certainty), remdesivir (2.6 days, moderate certainty), and lopinavir-ritonavir (1.2 days, low certainty). Hydroxychloroquine might increase the risk of adverse events compared with the other interventions, and remdesivir probably does not substantially increase the risk of adverse effects leading to drug discontinuation. No other interventions included enough patients to meaningfully interpret adverse effects leading to drug discontinuation.
Conclusion Glucocorticoids probably reduce mortality and mechanical ventilation in patients with covid-19 compared with standard care. The effectiveness of most interventions is uncertain because most of the randomised controlled trials so far have been small and have important study limitations.
DOI: 10.1136/bmj.m2980
Source: https://www.bmj.com/content/370/bmj.m2980
BMJ-British Medical Journal:《英国医学杂志》，创刊于1840年。隶属于BMJ出版集团，最新IF：93.333
官方网址：http://www.bmj.com/
投稿链接：https://mc.manuscriptcentral.com/bmj
本期文章：《英国医学杂志》：Online/在线发表
