Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada; National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
Lancet Microbe. 2022 Sep;3(9):e683-e692. doi: 10.1016/S2666-5247(22)00123-9. Epub 2022 Jul 5.
Specific treatments targeting Ebola virus are crucial in managing Ebola virus disease. To support the development of clinical practice guidelines on medications for Ebola virus disease, we aimed to evaluate the efficacy and safety of therapies for patients with Ebola virus disease.
In this systematic review and network meta-analysis, we searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Scopus, Global Health, African Index Medicus, World Health Organization Global Index Medicus, the Cumulative Index to Nursing and Allied Health Literature, ClinicalTrials.gov, Epistemonikos, bioRxiv, medRxiv, and SSRN without language restrictions for randomised controlled trials (RCTs) published between database inception and Jan 1, 2022, comparing at least one therapeutic agent for Ebola virus disease against standard care or another therapeutic agent for Ebola virus disease. Two reviewers assessed study eligibility and extracted summary data independently using a standardised form. Our outcomes of interest were mortality, adverse maternal outcomes, risk of onward transmission, duration of admission to a health-care facility, functional status after Ebola virus disease, serious adverse events from medication, adverse perinatal outcomes, time to symptom resolution, and time to viral clearance. We did frequentist network meta-analyses to estimate the effect of all interventions and applied the Grading of Recommendations Assessment, Development and Evaluation approach to rate the certainty of the evidence. We registered the protocol with PROSPERO, CRD42022296539.
We identified 7840 records through database searches, of which two RCTs with a total of 753 patients proved eligible. Only data on mortality, the duration of admission, serious adverse events, and time to viral clearance were available for meta-analysis. Compared with standard care, REGN-EB3 (relative risk [RR] 0·40, 95% CI 0·18 to 0·89; moderate certainty) and mAb114 (0·42, 0·19 to 0·93; moderate certainty) probably reduce mortality. Whether ZMapp (0·60, 0·28 to 1·26; very low certainty) and remdesivir (0·64, 0·29 to 1·39; very low certainty) reduce mortality compared with standard care is uncertain. With high certainty, REGN-EB3 reduces mortality compared with ZMapp (0·67, 0·52 to 0·88) and remdesivir (0·63, 0·49 to 0·82). With high certainty, mAb114 also reduces mortality compared with ZMapp (0·71, 0·55 to 0·91) and remdesivir (0·66, 0·52 to 0·84). Compared with standard care, REGN-EB3, mAb114, ZMapp, and remdesivir might have little or no effect on the time to viral clearance (mean difference ranged from -0·25 days to -1·14 days; low certainty). ZMapp might reduce the duration of admission compared with standard care (mean difference -2·02 days, 95% CI -4·05 to 0·01; low certainty). Findings for all comparisons suggested that there might be little or no difference in the prevalence of serious adverse events, but certainty was low or very low in all comparisons but one.
REGN-EB3 and mAb114 separately reduce mortality compared with ZMapp, remdesivir, or standard care in patients with Ebola virus disease. These findings suggest that health-care workers should prioritise the use of REGN-EB3 and mAb114 for patients with Ebola virus disease during future outbreaks.
WHO.
针对埃博拉病毒的特定治疗方法对于埃博拉病毒病的管理至关重要。为了支持制定关于埃博拉病毒病药物的临床实践指南，我们旨在评估治疗埃博拉病毒病患者的疗法的疗效和安全性。
在这项系统评价和网络荟萃分析中，我们检索了 MEDLINE、Embase、Cochrane 对照试验中心注册库、Scopus、全球卫生、非洲医学索引、世界卫生组织全球医学索引、护理和相关健康文献累积索引、ClinicalTrials.gov、Epistemonikos、bioRxiv、medRxiv 和 SSRN，检索时间为数据库成立至 2022 年 1 月 1 日，比较了至少一种埃博拉病毒病治疗药物与标准治疗或另一种埃博拉病毒病治疗药物的随机对照试验（RCT）。两位评审员使用标准化表格独立评估研究的纳入标准和提取汇总数据。我们感兴趣的结局是死亡率、不良母婴结局、传播风险、在医疗机构住院时间、埃博拉病毒病后的功能状态、药物的严重不良事件、不良围产期结局、症状缓解时间和病毒清除时间。我们进行了频率网络荟萃分析，以估计所有干预措施的效果，并应用推荐评估、制定和评估方法对证据的确定性进行评级。我们在 PROSPERO 上注册了该方案，CRD42022296539。
我们通过数据库检索共确定了 7840 条记录，其中两项共纳入 753 名患者的 RCT 符合纳入标准。仅有死亡率、住院时间、严重不良事件和病毒清除时间的数据可用于荟萃分析。与标准治疗相比，REGN-EB3（相对风险[RR]0·40，95%CI 0·18 至 0·89；中等确定性）和 mAb114（0·42，0·19 至 0·93；中等确定性）可能降低死亡率。ZMapp（0·60，0·28 至 1·26；极低确定性）和瑞德西韦（0·64，0·29 至 1·39；极低确定性）与标准治疗相比是否降低死亡率尚不确定。REGN-EB3 与 ZMapp（0·67，0·52 至 0·88）和瑞德西韦（0·63，0·49 至 0·82）相比，死亡率降低的确定性较高。mAb114 与 ZMapp（0·71，0·55 至 0·91）和瑞德西韦（0·66，0·52 至 0·84）相比，死亡率降低的确定性也较高。与标准治疗相比，REGN-EB3、mAb114、ZMapp 和瑞德西韦可能对病毒清除时间（平均差值范围为-0·25 天至-1·14 天；低确定性）几乎没有或没有影响。ZMapp 可能会缩短与标准治疗相比的住院时间（平均差值-2·02 天，95%CI-4·05 至 0·01；低确定性）。所有比较的结果均表明，严重不良事件的发生率可能几乎没有差异，但除了一项比较外，所有比较的确定性均较低或非常低。
REGN-EB3 和 mAb114 分别与 ZMapp、瑞德西韦或标准治疗相比，可降低埃博拉病毒病患者的死亡率。这些发现表明，在未来的埃博拉病毒病疫情中，医护人员应优先考虑使用 REGN-EB3 和 mAb114 治疗埃博拉病毒病患者。
世卫组织。
