TY - JOUR
T1 - Effects of therapies for Ebola virus disease
T2 - a systematic review and network meta-analysis
AU - Collaborators
AU - Gao, Ya
AU - Zhao, Yunli
AU - Guyatt, Gordon
AU - Fowler, Robert
AU - Kojan, Richard
AU - Ge, Long
AU - Tian, Jinhui
AU - Diaz, Janet
AU - Lado, Marta
AU - Youkee, Daniel
AU - Ahmad, Aasim
AU - Albertson, Cindy
AU - Caluwaerts, Séverine
AU - Camara, Modet
AU - Crozier, Ian
AU - De Clerck, Hilde
AU - Dunachie, Susanna
AU - Fischer, William A.
AU - Jamil, Bushra
AU - Kabongo, Patrice
AU - Kabuni, Patricia
AU - Ngorombi, Charline Kahambu
AU - Kakule, Maurice
AU - Kolié, Marie Claire
AU - Lakoh, Sulaiman
AU - Lang, Hans Jörg
AU - Moses, J. Soka
AU - Fiston, Isekusu Mpinda
AU - Mulumba, Philippe Mukumbayi
AU - Murthy, Srinivas
AU - Samura, Sorie
AU - Couban, Rachel
AU - Hao, Qiukui
N1 - Funding Information:
This work was supported by a WHO Health Emergencies Programme agreement for performance of work services (grant number 202793732). YG and YZ acknowledge funding from the China Scholarship Council. We thank members of the WHO Guideline Development Group for Therapeutics for Ebola Virus Disease for critical feedback on the research question, subgroup and outcome selection, and GRADE judgments: Janet Diaz (WHO, Geneva, Switzerland); Marta Lado (WHO, Geneva, Switzerland); and Daniel Youkee (WHO, Geneva, Switzerland). We thank Rachel Couban (librarian at McMaster University, Hamilton, ON, Canada) for helping to develop the search strategy. We thank Sorie Samura (National Emergency Medical Services, Freetown, Sierra Leone) and Maurice Kakule (Mangodomu Reference Health Centre, Kinshasa, Democratic Republic of the Congo) for contributing to the outcome prioritisation survey. We thank Tyler Bonnett (Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA) for providing additional data from the PALM trial.
Funding Information:
This work was supported by a WHO Health Emergencies Programme agreement for performance of work services (grant number 202793732). YG and YZ acknowledge funding from the China Scholarship Council. We thank members of the WHO Guideline Development Group for Therapeutics for Ebola Virus Disease for critical feedback on the research question, subgroup and outcome selection, and GRADE judgments: Janet Diaz (WHO, Geneva, Switzerland); Marta Lado (WHO, Geneva, Switzerland); and Daniel Youkee (WHO, Geneva, Switzerland). We thank Rachel Couban (librarian at McMaster University, Hamilton, ON, Canada) for helping to develop the search strategy. We thank Sorie Samura (National Emergency Medical Services, Freetown, Sierra Leone) and Maurice Kakule (Mangodomu Reference Health Centre, Kinshasa, Democratic Republic of the Congo) for contributing to the outcome prioritisation survey. We thank Tyler Bonnett (Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA) for providing additional data from the PALM trial.
Publisher Copyright:
© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
PY - 2022/9
Y1 - 2022/9
N2 - Background: 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. Methods: 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. Findings: 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. Interpretation: 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. Funding: WHO.
AB - Background: 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. Methods: 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. Findings: 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. Interpretation: 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. Funding: WHO.
UR - http://www.scopus.com/inward/record.url?scp=85137278416&partnerID=8YFLogxK
U2 - 10.1016/S2666-5247(22)00123-9
DO - 10.1016/S2666-5247(22)00123-9
M3 - Article
AN - SCOPUS:85137278416
SN - 2666-5247
VL - 3
SP - e683-e692
JO - The Lancet Microbe
JF - The Lancet Microbe
IS - 9
ER -
