The anti-inflammatory drug hydroxychloroquine should not be used to prevent infection in people who do not have covid-19, says a World Health Organisation (WHO) Guideline Development Group (GDG) panel of experts. Their strong recommendation is based on high certainty evidence from six randomised controlled trials involving over 6,000 participants with and without known exposure to a person with COVID-19 infection.
High certainty evidence showed that hydroxychloroquine had no meaningful effect on death and admission to hospital, while moderate certainty evidence showed that hydroxychloroquine had no meaningful effect on laboratory confirmed COVID-19 infection and it probably increases the risk of adverse effects.
As such, the panel considers that this drug is no longer a research priority and that resources should be used to evaluate other more promising drugs to prevent COVID-19.
This guideline applies to all individuals who do not have COVID-19, regardless of their exposure to a person with covid-19 infection.
The panel judged that almost all people would not consider this drug worthwhile, and also decided that factors such as resources, feasibility, acceptability, and equity for countries and healthcare systems were unlikely to alter the recommendation.
Today’s recommendation is the first version of a living guideline for drugs to prevent COVID-19, developed by the World Health Organisation with the methodological support of MAGIC Evidence Ecosystem Foundation.
It’s aim is to provide trustworthy guidance on the management of COVID-19 and help doctors make better decisions with their patients.
Living guidelines are useful in fast moving research areas like COVID-19 because they allow researchers to update previously vetted and peer reviewed evidence summaries.
New recommendations for other preventive drugs for COVID-19 will be added to this guideline as more evidence becomes available.
Study details
A living WHO guideline on drugs to prevent COVID-19
François Lamontagne, Thomas Agoritsas, Reed Siemieniuk, Bram Rochwerg, Jessica Bartoszko, Lisa Askie, Helen Macdonald, Wagdy Amin, Frederique Jacquerioz Bausch, Erlina Burhan, Maurizio Cecconi, Duncan Chanda, Vu Quoc Dat, Bin Du, Heike Geduld, Patrick Gee, Harley Nerina, Madiha Hashimi, Beverley J Hunt, Sushil Kabra, Seema Kanda, Leticia Kawano-Dourado, Yae-Jean Kim, Niranjan Kissoon, Arthur Kwizera, Yee-Sin Leo, Imelda Mahaka, Hela Manai, Greta Mino, Emmanuel Nsutebu, Natalia Pshenichnaya, Nida Qadir, Shalini Sri Ranganathan, Saniya Sabzwari, Rohit Sarin, Michael Sharland, Yinzhong Shen, Joao Paulo Souza, Miriam Stegemann, Sebastian Ugarte, Sridhar Venkatapuram, Dubula Vuyiseka, Jacobus Preller, Romina Brignardello-Petersen, Elena Kum, Anila Qasim, Dena Zeraatkar, Andrew Owen, Gordon Guyatt, Lyubov Lytvyn, Janet Diaz, Per Olav Vandvik, Michael Jacob
Published in BMJ on 2 March 2021
Abstract
Clinical question
What is the role of drugs in preventing covid-19?
Why does this matter?
There is widespread interest in whether drug interventions can be used for the prevention of covid-19, but there is uncertainty about which drugs, if any, are effective. The first version of this living guideline focuses on the evidence for hydroxychloroquine. Subsequent updates will cover other drugs being investigated for their role in the prevention of covid-19.
Recommendation
The guideline development panel made a strong recommendation against the use of hydroxychloroquine for individuals who do not have covid-19 (high certainty).
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 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 linked systematic review and network meta-analysis (6 trials and 6059 participants) found that hydroxychloroquine had a small or no effect on mortality and admission to hospital (high certainty evidence). There was a small or no effect on laboratory confirmed SARS-CoV-2 infection (moderate certainty evidence) but probably increased adverse events leading to discontinuation (moderate certainty evidence). The panel judged that almost all people would not consider this drug worthwhile. In addition, the panel decided that contextual factors such as resources, feasibility, acceptability, and equity for countries and healthcare systems were unlikely to alter the recommendation. The panel considers that this drug is no longer a research priority and that resources should rather be oriented to evaluate other more promising drugs to prevent covid-19.
Updates
This is a living guideline. New recommendations will be published in this article and signposted by update notices to this guideline.
Readers note
This is the first version of the living guideline for drugs to prevent covid-19. It complements the WHO living guideline on drugs to treat covid-19. When citing this article, please consider adding the update number and date of access for clarity.
[link url="https://www.bmj.com/company/newsroom/who-expert-panel-strongly-advises-against-use-of-hydroxychloroquine-to-prevent-covid-19/"]BMJ material[/link]
[link url="https://www.bmj.com/content/372/bmj.n526"]BMJ study (Open access)[/link]
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[link url="https://www.medicalbrief.co.za/archives/hydroxychloroquine-plus-azithromycin-doubles-cardiovascular-mortality-risk/"]Hydroxychloroquine plus azithromycin doubles cardiovascular mortality risk[/link]
[link url="https://www.medicalbrief.co.za/archives/hydroxychloroquine-as-a-covid-19-treatment-not-recommended-by-sas-doh-and-private-sector/"]Hydroxychloroquine as a COVID-19 treatment not recommended by SA’s DoH and private sector[/link]
[link url="https://www.medicalbrief.co.za/archives/who-discontinues-hydroxychloroquine-and-lopinavir-ritonavir-treatment-arms-for-covid-19/"]WHO discontinues hydroxychloroquine and lopinavir/ritonavir treatment arms for COVID-19[/link]
[link url="https://www.medicalbrief.co.za/archives/fda-revokes-emergency-use-authorisation-for-chloroquine-phosphate-and-hydroxychloroquine-sulfate/"]FDA revokes emergency use authorisation for chloroquine phosphate and hydroxychloroquine sulfate[/link]