Hydroxychloroquine: the WHO strongly advises against it for prevention

SUMMARY :

Hydroxychloroquine: the association with azithromycin increases the risk of death
Hydroxychloroquine: no antiviral effect in vivo
Hydroxychloroquine: the dubious study of The Lancet magazine
Chloroquine: cardiac side effects?
Plaquenil and chloroquine: which patients?
What is the difference between chloroquine and hydroxychloroquine?

“The anti-inflammatory drug hydroxychloroquine should not be used as a preventive treatment by people who do not have Covid-19” has just announced a group of experts from the World Health Organization (WHO) in recommendations published by the British medical journal. This recommendation is based on the results of six controlled and randomized trials involving nearly 6000 participants. “ Research has shown with certainty that hydroxychloroquine has no significant effect on the risk of death or hospital admission, while other research has shown that hydroxychloroquine has no effect on the number of laboratory-confirmed positive Covid-19 cases reported and that it probably increases the risk of ‘adverse effects’ explain the experts.

Hydroxychloroquine: the association with azithromycin increases the risk of death

An extensive meta-analysis, published August 27 in the journal Clinical Microbiology and Infection, concludes that it is ineffective. A total of 29 scientific studies evaluating the molecule, whether or not associated with azithromycin, were reviewed. And these are 11,000 patients treated with hydroxychloroquine alone, more than 8,000 in combination with azithromycin and 12,000 other “control group” without either of the two treatments who were included in the treatment. ©ta-analysis. Recorded death rates were compared to that seen in the largest cohort of hospitalized patients with Covid-19 in Europethe British Isaric cohort, which in June indicated a mortality rate of 26% among some 26,000 people hospitalized.

Result: no significant difference for mortality rates with hydroxychloroquine alone. In contrast, patients who received a cocktail combining hydroxychloroquine and azithromycin have an increased risk of death of 7% compared to those who received only conventional treatments.

Conclusion, “hydroxychloroquine alone is not effective in the treatment of Covid-19, and its combination with azithromycin increases the risk of mortality”, summarize the authors, who invite not to pursue studies. studies evaluating the controversial molecule.

Hydroxychloroquine: no antiviral effect in vivo

This July 22, the results of preclinical study launched in February 2020, showed that hydroxychloroquine, which has antiviral properties in certain in vitro tests (using cells in culture), has no antiviral efficacy in vivo. This study aimed to evaluate the effects of hydroxychloroquine, combined or not with azithromycin, in a model of Covid-19 infection in macaques (the disease observed in non-human primates being very similar to that observed in the majority of patients with COVID-19). It brought together scientists from the CEA, Inserm, the Institut Pasteur, the CNRS, the University of Paris-Saclay, the AP-HM, the University Claude Bernard Lyon 1 and Aix-Marseille University.

Different treatment strategies have been tested, with or without azithromycin (an antibiotic often associated). The conclusions, published in the scientific journal Naturehas no antiviral effect against the SARS-CoV-2 virus, whether before infection to reduce the viral load or during the first days after infection.

Hydroxychloroquine: the dubious study of The Lancet magazine

This June 4, the medical journal The Lancet proceeded to the retraction of his article which suggested that hydroxychloroquine, associated or not with an antibiotic (azithromycin), increased mortality and cardiac arrhythmias in patients hospitalized for Covid- 19. Indeed, three of the four authors of the study had retracted. They lamented that they could no longer vouch for the “veracity” of their primary data provided by the American company Surgisphere.

The New England Journal of Medicine (NEJM) had also withdrawn an article published on May 1, which concluded that taking antihypertensive treatments had no influence on the severity of Covid-19. For both studies, the lead author is Mandeep Mehra (Harvard Medical School) and the data came from Surgisphere.

What are the conclusions of the Lancet study? The study in question is a retrospective analysis of the medical records of more than 96,000 patients hospitalized between December 20, 2019 and April 14, 2020, in 671 hospitals, for cause of Covid-19.

About 15,000 had been treated with chloroquine or hydroxychloroquine alone or in combination with azithromycin. These groups of patients, divided into 4 groups, were compared to a control group comprising more than 80,000 patients who had not received treatment. As a result, the four treatments were associated with a higher risk of mortality than in the control group (which was 9.3%): 16.4% of deaths for chloroquine alone, 22.2% when it was combined with the antibiotic, 18% for hydroxychloroquine alone, and 23.8% when it was associated with the same antibiotic.

Closing? Far from providing any benefit to hospitalized patients, chloroquine and hydroxychloroquine, whether or not combined with an antibiotic (including azithromycin), lead to an increased risk of cardiac arrhythmia and death in hospital according to this study. A study with a clearly unfavorable comment from its lead author, Dr. Mandeep R. Mehra: “This is the first large-scale study to find statistically strong evidence that treatment with chloroquine or hydroxychloroquine does not benefit patients with COVID-19.Instead, our results suggest that it may be associated with an increased risk serious heart problems and an increased risk of death.” He continued with two recommendations: confirm these results through a randomized clinical trial and suspend its use outside of any trial.

Following this publication, many countries stopped prescribing hydroxychloroquine in the treatment of coronavirus.

After the publication of the study, the High Council for Public Health (HCSP) recommended that hydroxychloroquine should no longer be used in the treatment of coronavirus and the government repealed the derogatory provisions authorizing the prescription of hydroxychloroquine. As a reminder, these provisions were the subject of a decree published at the end of March allowing doctors caring for patients with Covid-19 in hospitals to prescribe them hydroxychloroquine. “Whether in town or in the hospital, this molecule should not be prescribed for patients with COVID-19”, is it specified in a press release the Ministry of Health. Health.

The Medicines Agency had announced its wish to suspend clinical trials evaluating hydroxychloroquine in patients with Covid-19, as had the World Health Organization (WHO ). “This measure comes pending new data on the use of hydroxychloroquine in patients with COVID-19” underlines the ANSM. But patients undergoing treatment within the framework of these clinical trials can continue it until the end of the protocol.

“The internal evidence from the Solidarity/Discovery Trial, the external evidence from the Recovery Trial, and the combined evidence from these two largely random trials, taken together, suggests that hydroxychloroquine does not result in reduced patient mortality,” said WHO’s Dr Ana Maria Henao Restrepo.

Very quickly, more than 120 scientists around the world had expressed doubts about the seriousness of the studythrough an open letter to the editor of the scientific journal The Lancet. In France, Professor Didier Raoult hastened to describe it as “messy”, stressing in particular that it was not possible to obtain such homogeneity between patients of 5 different continents. In their open letters, these scientists (who do not all advocate the use of hydroxychloroquine in the treatment of coronavirus) asked that the WHO or another independent institution validate the conclusions of this study and that the data is made available as open data.

Chloroquine: cardiac side effects?

The molecule is suspected of causing electrical abnormalities in the functioning of the heart which can lead to heart rhythm disorderseven at death.

The Medicines Agency (ANSM), which collects reports of adverse drug-related effects, pointed out at the end of April that they were on the increase. In total 321 cases in connection with the Covid-19 infection had been notified, including 80% of serious cases and 4 deaths, the “signal of vigilance” is therefore confirmed indicated the ANSM.

The independent review Prescrire had announced a few days earlier to be unfavorable to the use of hydroxychloroquine (Plaquénil) in combination with azithomycin in the treatment of Covid-19 because this combination “increases the risk of serious arrhythmias cardiac: prolongation of the QT interval with high risk of cardiac arrhythmia and torsades de pointes”.

What is the difference between chloroquine and hydroxychloroquine?

Chloroquine is a drug mainly prescribed for the treatment or prevention of malaria (the famous Nivaquine). Hydroxychloroquine is one of its derivatives, which is essentially prescribed in rheumatology to treat lupus or rheumatoid arthritis. It is also prescribed for the prevention of summer light eruption. This medication is marketed in France under the name Plaquenil. Both are old drugs that were developed between the two world wars by German chemists. Both marketed by the Sanofi laboratory, obtained their MA (marketing authorization) in 1998 for Nivaquine and in 2004 for Plaquenil.

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