WHO Therapeutics and COVID-19. Living Guidelines 20 November 2020
SUMMARY: WHAT IS THIS LIVING GUIDELINE?
Clinical question: What is the role of drugs in the treatment of patients with COVID-19?
Target audience: The target audience is clinicians and health care decision-makers.
Current practice: Current practice to treat COVID-19 is variable, reflecting large-scale uncertainty. Numerous randomized controlled trials (RCTs) of many different drugs are underway to inform practice. This version of the World Health Organization (WHO) living guideline contains new information and recommendations on remdesivir. It follows the preprint publication of results from the WHO SOLIDARITY trial on 15 October 2020 (1), which also reported results on hydroxychloroquine and lopinavir-ritonavir. Remdesivir is increasingly used to treat patients hospitalized with COVID-19 and is of considerable interest to all stakeholder groups.
Recommendations: The panel made a conditional recommendation against the use of remdesivir in hospitalized patients with COVID-19, regardless of disease severity. This guidance adds to recommendations published in the previous version: a strong recommendation for systemic corticosteroids in patients with severe and critical COVID- 19, and a conditional recommendation against systemic corticosteroids in patients with non-severe COVID-19.
How this guideline was created: This living guideline is an innovation from WHO, driven by the urgent need for global collaboration to provide trustworthy and evolving COVID-19 guidance informing policy and practice worldwide.
WHO has partnered with the non-profit Magic Evidence Ecosystem Foundation (MAGIC) for methodologic
support and development and dissemination of living guidance for COVID-19 drug treatments, based on a living systematic review and network analysis (2). An international Guideline Development Group (GDG) of content experts, clinicians, patients, ethicists and methodologists produced recommendations following standards for trustworthy guideline development using the Grading of Recommendations Assessment, Development an Evaluation (GRADE) approach. No conflict of interest was identified for any panel member.
The latest evidence: The recommendation on remdesivir was informed by results from a systematic review and network meta-analysis (NMA) that pooled data from four randomized trials with 7333 participants hospitalized for COVID-19. The resulting GRADE evidence summary suggested that remdesivir has possibly no effect on mortality (odds ratio 0.90, 95% confidence interval [CI] 0.70 - 1.12; absolute effect estimate 10 fewer deaths per 1000 patients, 95% CI from 29 fewer - 11 more deaths per 1000 patients; low certainty evidence); and possibly no effect on the other important outcomes identified by the panel, with similar low to very low certainty of evidence. The panel judged the overall credibility of subgroup analyses assessing differences in mortality by severity of illness to be insufficient to make subgroup recommendations.
Understanding the recommendations: When moving from evidence to the conditional recommendation against the use of remdesivir in hospitalized patients with COVID-19, the panel emphasized the evidence suggesting no important effect on mortality, need for mechanical ventilation, time to clinical improvement, and other patientimportant outcomes. Considering the low or very low certainty evidence for all outcomes, the panel concluded that the evidence did not prove that remdesivir has no benefit; rather, there is no evidence based on currently available data that it does improve patient-important outcomes. The panel placed low value on small and uncertain benefits in the presence of the remaining possibility of important harms. In addition, the panel considered contextual factors such as resources, feasibility, acceptability and equity for countries and health care systems.