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Clinical question What is the role of drug interventions in the treatment of patients with covid-19?
New recommendation Increased attention on ivermectin as a potential treatment for covid-19 triggered this recommendation. The panel made a recommendation against ivermectin in patients with covid-19 regardless of disease severity, except in the context of a clinical trial.
Prior recommendations (a) a strong recommendation against the use of hydroxychloroquine in patients with covid-19, regardless of disease severity; (b) a strong recommendation against the use of lopinavir-ritonavir in patients with covid-19, regardless of disease severity; (c) a strong recommendation for systemic corticosteroids in patients with severe and critical covid-19; (d) a conditional recommendation against systemic corticosteroids in patients with non-severe covid-19, and (e) 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 analysis informed the recommendations. An international guideline development group (GDG) 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 There is insufficient evidence to be clear to what extent, if any, ivermectin is helpful or harmful in treating covid-19. There was a large degree of uncertainty in the evidence about ivermectin on mortality, need for mechanical ventilation, need for hospital admission, time to clinical improvement, and other patient-important outcomes. There is potential for harm with an increased risk of adverse events leading to study drug discontinuation. Applying pre-determined values and preferences, the panel inferred that almost all well informed patients would want to receive ivermectin only in the context of a randomised trial, given that the evidence left a very high degree of uncertainty on important effects.
Updates This is a living guideline. It replaces earlier versions (4 September, 20 November, and 17 December 2020) 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 fourth version (update 3) of the living guideline (BMJ 2020;370:m3379). When citing this article, please consider adding the update number and date of access for clarity.
This living guideline responds to emerging evidence from randomised controlled trials (RCTs) on existing and new drug treatments for covid-19. Although case numbers are falling in some regions, they are rising in others. Vaccines are linked to falling case numbers and hospitalisations, but most people remain unvaccinated. It is unclear how long protection following vaccination or natural infection will last, or how this might alter with the emergence of new variants. Therefore, the potential for drugs to treat people infected with covid-19 remains of interest and is the focus of this guideline. A linked guideline addresses the role of drugs in the prevention of covid-19 among people who are not infected.
More than 3800 trials on covid-19 interventions have been registered or are ongoing (see section on emerging evidence2). Among these are large national and international platform trials (such as RECOVERY, WHO SOLIDARITY, DISCOVERY, REMAP-CAP and ACTIV) that recruit large numbers of patients in many countries, with a pragmatic and adaptive design. These platform trials are currently investigating and reporting on numerous interventions, including antiviral monoclonal antibodies and immunomodulators. This rapidly evolving evidence landscape requires trustworthy interpretation and expeditious clinical practice guidelines to inform clinicians and health care decision-makers.
A living network meta-analysis associated with this guideline will incorporate new trial data as the evidence base increases and allows for analysis of comparative effectiveness of multiple covid-19 treatments.5 This network meta-analysis and other related publications are included in. We also use additional relevant evidence on safety, prognosis, and patient values and preferences related to covid-19 treatments to inform the living guidance.
Créditos: Comité científico Covid