Attachments
Executive summary
Clinical question: What is the role of virus-specific therapeutics in the treatment of patients with Ebola virus disease (EVD), caused by Ebola virus (EBOV; Zaire ebolavirus)?
Context: The limited evidence base for therapeutics for EVD was augmented by the publication of the Pamoja Tulinde Maisha (PALM) randomized controlled trial (RCT) in 2019, which compared ZMapp with three investigational agents: remdesivir, REGN-EB3 and mAb114. This guideline reviews the existing evidence and provides recommendations for use of EBOV-specific therapeutics in patients with EVD.
Target audience: Health care providers caring for patients with EVD and policy-makers involved in EVD preparedness and response.
Methods: A systematic review and meta-analysis of RCTs of therapeutics for EVD was conducted.
Recommendations based on the synthesized evidence were made by the GDG using GRADE methodology.
New recommendations: The GDG made the following recommendations:
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Strong recommendation for treatment with mAb114 or REGN-EB3 for patients with realtime polymerase chain reaction (RT-PCR) confirmed EVD and for neonates of unconfirmed EVD status, 7 days or younger, born to mothers with confirmed EVD;
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Conditional recommendation against treatment with remdesivir for patients with RT-PCR confirmed EVD;
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Conditional recommendation against treatment with ZMapp for patients with RT-PCR confirmed EVD.
Availability: Access to these therapeutics is challenging and pricing and future supply remain unknown, especially in resource-poor areas. Without concerted effort, access will remain limited, and it is therefore possible that this strong recommendation could exacerbate health inequity. Therefore, given the demonstrated benefits for patients, these recommendations should act as a stimulus to engage all possible mechanisms to improve global access to these treatments.
About this guideline: This guideline from WHO incorporates the latest high-quality evidence and provides new recommendations on EBOV-specific therapeutics for EVD. The GDG typically evaluates a drug when WHO judges sufficient evidence is available to make a recommendation. While the GDG takes an individual patient perspective in making recommendations, it also considers resources implications, acceptability, feasibility, equity and human rights. This guideline was developed according to standards and methods for trustworthy guidelines.
Nomenclature: To facilitate comprehension, this guideline maintained the therapeutic names as they were described in the relevant RCTs and other peer-reviewed publications.