伊维菌素和多西环素单药及联合治疗 COVID-19 的安全性和疗效：范围综述。
Safety and Efficacy of Ivermectin and Doxycycline Monotherapy and in Combination in the Treatment of COVID-19: A Scoping Review.
机构信息
Department of Pharmacology, KPC Medical College and Hospital, Kolkata, India.
MarksMan Healthcare Communications and KYT Adhere, H. No 9-1-67, Plot no. 67, TNGO's colony, Behind Q City, Financial District, Hyderabad, Telangana, 500032, India.
出版信息
Drug Saf. 2021 Jun;44(6):635-644. doi: 10.1007/s40264-021-01066-y. Epub 2021 Apr 16.
INTRODUCTION AND OBJECTIVE
Ivermectin (IVM) and doxycycline (DOXY) have demonstrated in-vitro activity against SARS-CoV-2, and have a reasonable safety profile. The objective of this systematic review was to explore the evidence in the literature on the safety and efficacy of their use as monotherapy and combination therapy in COVID-19 management.
METHODS
After prospectively registering the study protocol with the Open Science Framework, we searched PubMed, Google Scholar, clinicaltrials.gov, various pre-print servers and reference lists for relevant records published until 16 February, 2021 using appropriate search strategies. Baseline features and data pertaining to efficacy and safety outcomes were extracted separately for IVM monotherapy, DOXY monotherapy, and IVM + DOXY combination therapy. Methodological quality was assessed based on the study design.
RESULTS
Out of 200 articles screened, 19 studies (six retrospective cohort studies, seven randomised controlled trials, five non-randomised trials, one case series) with 8754 unique patients with multiple stages of COVID-19 were included; four were pre-prints and one was an unpublished clinicaltrials.gov document. The comparator was standard care and 'hydroxychloroquine + azithromycin' in seven and three studies respectively, and two studies were placebo controlled; six studies did not have a comparator. IVM monotherapy, DOXY monotherapy and IVM + DOXY were explored in eight, five and five studies, respectively; one study compared IVM monotherapy and IVM + DOXY with placebo. While all studies described efficacy, the safety profile was described in only six studies. Efficacy outcomes were mixed with some studies concluding in favour of the intervention and some studies displaying no significant benefit; barring one study that described 9/183 patients with erosive esophagitis and non-ulcer dyspepsia with IVM + DOXY (without causality assessment details), there were no new safety signals of concern with any of the three interventions considered. The quality of studies varied widely, with five studies having a 'good' methodological quality.
CONCLUSIONS
Evidence is not sufficiently strong to either promote or refute the efficacy of IVM, DOXY, or their combination in COVID-19 management.
SYSTEMATIC REVIEW PROTOCOL REGISTRATION DETAILS
Open Science Framework: https://osf.io/n7r2j .
简介和目的
伊维菌素（IVM）和多西环素（DOXY）已在体外显示出对 SARS-CoV-2 的活性，且具有合理的安全性。本系统综述的目的是探索文献中关于它们在 COVID-19 管理中单药和联合治疗的安全性和疗效的证据。
方法
在预注册研究方案后，我们使用适当的搜索策略，前瞻性地在 PubMed、Google Scholar、clinicaltrials.gov、各种预印本服务器和参考文献列表中搜索截至 2021 年 2 月 16 日发表的相关记录。分别提取 IVM 单药治疗、DOXY 单药治疗和 IVM+DOXY 联合治疗的基线特征和疗效及安全性结局数据。根据研究设计评估方法学质量。
结果
在筛选的 200 篇文章中，纳入了 19 项研究（6 项回顾性队列研究、7 项随机对照试验、5 项非随机试验、1 项病例系列），共涉及 8754 例患有多种阶段 COVID-19 的患者，其中 4 项为预印本，1 项为未发表的 clinicaltrials.gov 文档。比较组是标准治疗和 7 项研究中的“羟氯喹+阿奇霉素”、3 项研究中的“多西环素”，2 项研究是安慰剂对照；6 项研究没有比较组。IVM 单药治疗、DOXY 单药治疗和 IVM+DOXY 联合治疗分别在 8、5 和 5 项研究中进行了探讨；1 项研究将 IVM 单药治疗和 IVM+DOXY 联合治疗与安慰剂进行了比较。虽然所有研究都描述了疗效，但只有 6 项研究描述了安全性概况。疗效结果参差不齐，一些研究认为干预有效，一些研究则没有显示出显著益处；除了一项研究描述了 183 例患者中有 9 例出现 IVM+DOXY 相关的侵蚀性食管炎和非溃疡性消化不良（未评估因果关系细节），考虑到这三种干预措施，没有新的安全性信号令人担忧。研究质量差异很大，5 项研究具有“良好”的方法学质量。
结论
目前的证据不足以支持或反驳 IVM、DOXY 或其在 COVID-19 管理中的联合治疗的疗效。
系统综述方案注册详情
Open Science Framework：https://osf.io/n7r2j。
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