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A Living WHO Guideline on Drugs for COVID-19 (Update 4)

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Correspondence to: Bram Rochwerg rochwerg@mcmaster.ca or Michael Jacobs michael.jacobs@ucl.ac.uk

Abstract

Clinical question: What is the role of drug interventions in the treatment of patients with covid-19?

New recommendation: The publication of the RECOVERY and REMAP-CAP randomised controlled trials triggered this guideline update, resulting in a strong recommendation for interleukin-6 (IL-6) receptor blockers (tocilizumab or sarilumab) in patients with severe or critical covid-19.

Prior recommendations: (a) A recommendation not to use ivermectin in patients with covid-19, regardless of disease severity, except in the context of a clinical trial; (b) a strong recommendation against the use of hydroxychloroquine in patients with covid-19, regardless of disease severity; (c) a strong recommendation against the use of lopinavir-ritonavir in patients with covid-19, regardless of disease severity; (d) a strong recommendation for systemic corticosteroids in patients with severe and critical covid-19; (e) a conditional recommendation against systemic corticosteroids in patients with non-severe covid-19; and (f) a conditional recommendation against remdesivir in hospitalised patients with covid-19.

How this guideline was created: This living guideline is from the World Health Organization (WHO) and provides up to date covid-19 guidance to inform policy and practice worldwide. Magic Evidence Ecosystem Foundation (MAGIC) provided methodological support. A living systematic review with network meta-analysis informed the recommendations. For IL-6 receptor blockers, a complementary prospective meta-analysis informed the outcome of mortality. An international guideline development panel of content experts, clinicians, patients, an ethicist and methodologists produced recommendations following standards for trustworthy guideline development using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Understanding the new recommendation: The panel judged that almost all well informed patients would want to receive IL-6 receptor blockers (tocilizumab and sarilumab) for severe and critical covid-19, given that there was high certainty evidence of benefit for mortality and mechanical ventilation, the two most important outcomes for patients. In addition to the network analysis, a direct comparison from REMAP-CAP provided evidence that tocilizumab and sarilumab had similar effects on the main outcomes of interest. There is ongoing uncertainty about serious adverse events and bacterial infections related to IL-6 receptor blockers. The panel recognised important resources and access issues around IL-6 receptor blockers.

Updates: This is a living guideline. It replaces earlier versions (4 September, 20 November, 17 December 2020, and 31 March 2021) and supersedes the BMJ Rapid Recommendations on remdesivir published on 2 July 2020. The previous versions can be found as data supplements. New recommendations will be published as updates to this guideline.

Readers note: This is the fifth version (update 4) of the living guideline (BMJ 2020;370:m3379). When citing this article, please consider adding the update number and date of access for clarity.