While the epidemic which has paralyzed part of the planet continues to wreak havoc on all continents, timidly starting a slow decline, no treatment specific has not yet been proven, and the molecules a time perceived as the most promising disappointed expectations. Over-publicized for months, the hydroxychloroquine of Pr Didier Raoult, praised by the American and Brazilian presidents Donald Trump and Jair Bolsonaro as a “miracle cure”, will ultimately not demonstrate the slightest impact.
A new meta-analysis, published this Thursday in the journal Clinical Microbiology and Infection, the official journal of the European Society for Clinical Microbiology and Infectious Diseases (ESCMID), concludes that it is ineffective. “Our results confirm a trend already observed in other studies, which suggests that hydroxychloroquine, whether or not associated with azithromycin, does not reduce mortality in hospitalized patients ”, confides its principal author Thibault Fiolet, epidemiologist and doctoral student in health public at Inserm-University Paris Saclay.
Read also Covid-19: the European Commission decides against Didier Raoult
The authors reviewed 29 studies evaluating the effects of chloroquine or hydroxychloroquine, combined or not with the antibiotic azithromycin, on patients with Covid-19. Among them, three randomized controlled trials, one non-randomized trial, and 25 observational studies, including those conducted by Professor Raoult’s team at the IHU in Marseille. Ten of them, the authors note, were at risk of “critical” bias. The meta-analysis includes, once the less reliable studies have been excluded, 11,932 patients treated with hydroxychloroquine alone, 8,081 patients who received in combination hydroxychloroquine and azithromycin, group control grouping 12,930 patients who received neither of the two molecules. The recorded mortality rates were compared to that observed among the largest cohort of hospitalized patients with Covid-19 in Europe, the British Isaric cohort, which in June indicated a death rate of 26% among some 26,000 people hospitalized.
Hydroxychloroquine-azithromycin cocktail increases risk of mortality by 7%
In the end, the study found no difference in disease outcome in patients who received a treatment with hydroxychloroquine. “Some observational studies indicate lower mortality, but randomized trials show a reverse trend, with an increased risk of death in treated patients. The difference is not significant, ”explains Thibault Fiolet.
In contrast, patients who received a cocktail combining hydroxychloroquine and azithromycin (the treatment recommended by Prof. Raoult) present an increased risk of death of 7% compared to those who received only conventional treatments. Unsurprisingly: the risks of cardiac toxicity associated with overdose of chloroquine are well known, and likely to be increased by azithromycin, itself cardiotoxic.
It is a pity that the IHU in Marseille, in particular, did not produce better quality studies …
The strength of this meta-analysis lies in its breadth: “The previous ones included only six or seven studies, and did not take into account in their models the differences in age, sex or co-morbidity between the different groups”, underlines Thibault Fiolet. “We also processed the data with two statistical approaches, and obtained the same results. However, it has weaknesses, with each study including patients at various stages of the disease and giving them disparate, not always documented, doses of treatment. “It is a pity that the IHU in Marseille, in particular, has not produced better quality studies …” regrets Thibault Fiolet. The emerging trend remains “clear”, write the authors: “Hydroxychloroquine alone is not effective in the treatment of Covid-19, and its combination with azithromycin increases the risk of mortality. […] We results suggest that there is no need for further studies evaluating these molecules. “
A tip that various authorities, in the world, have already followed: for lack of results and given a benefit-risk balance deemed unfavorable, France in May banned the use of hydroxychloroquine in the treatment of Covid-19, like the American Medicines Agency (FDA), which withdrew in June permission to use it in emergency. WHO has discontinued the hydroxychloroquine arm of its international Recovery trial. Hopes today are for other types of treatment: remdesivir, an antiviral that has shown encouraging (albeit timid) results in patients with the severe form of the disease, and dexamethasone, used in the treatment of asthma, which may help patients on ventilators.
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