It fascinates some, annoys many others, has already been the subject of dozens of scientific studies and can also cause serious undesirable effects in certain cases. Hydroxychloroquine, popularized by Marseille professor Didier Raoult, has been at the heart of all attention since the coronavirus spread around the world, starting with France.
This molecule would treat patients with Covid-19, according to the director of the IHU Mediterranean. False, answers a very large part of the medical and scientific class which is based on the results of numerous studies unveiled since March, including two published this Thursday in the British medical journal BMJ. "If hydroxychloroquine had a massive effect, given all the elements we already have, we would know," said Professor Olivier Bouchaud, head of the infectious diseases department at Avicenne hospital in Bobigny. We take stock.
What do the latest studies say?
These two studies published on Thursday conclude that hydroxychloroquine is not effective. For the first, 181 adult patients hospitalized and requiring oxygen were selected. 84 of them received hydroxychloroquine daily, unlike the other 97. The results are similar in these two groups of patients, either for the transfer rate in intensive care or for that of mortality. In summary, they "do not support the use (of hydroxychloroquine) in patients admitted to hospital who require oxygen", conclude French researchers from several hospitals in the Paris region, including Henri Mondor in Créteil.
"For the moment, there is no argument in favor of the use of hydroxychloroquine, even if certain studies show a minimal result", underlines with the Parisian Professor Jean-Daniel Lelièvre, head of the department of infectious diseases to Henri-Mondor.
2 new # COVID19 hydroxychloroquine trials, one randomized: no gohttps: //t.co/FzUuGK3Qfchttps: //t.co/fgEiQgYhKg@bmj_latest
How many more trials before the drug proponents give up? pic.twitter.com/klRdaYc93C
Previous work has also experimented with the association of hydroxychloroquine with azithromycin (an antibiotic), advocated by Pr Raoult. According to the results of one of these studies published on May 10 in the Journal of the American Medical Association (JAMA), hydroxychloroquine, azithromycin or the combination of the two are "not significantly associated with differences in mortality" by report to patients who had not received these drugs. Previous work has concluded similar findings. And this combination would also increase the risk of serious adverse cardiac effects.
What is wrong with these studies?
These works are sometimes criticized by the supporters of Pr Raoult, even by himself. On the one hand, some studies are only at the pre-publication stage. They have not yet been reread and validated by a reading committee of a medical journal. "In theory, you should always wait for an evaluation by experts from the magazine to whom the article was sent before mediating the results," said Professor Bouchaud.
PODCAST. Coronavirus: who is Didier Raoult, convinced that he has the miracle cure?
Other studies are based on a small number of patients, which would statistically reduce the possibility of demonstrating a possible positive effect (or its absence). The same applies when the groups with and without hydroxychloroquine are composed of patients with different profiles.
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Professor Raoult also criticizes certain studies for testing only hydroxychloroquine alone, while advocating the association with azithromycin. He also highlighted, this Friday morning, an extract from the study of French researchers published in the journal BMJ. It states that "none of the 15 patients who received a combination of hydroxychloroquine and azithromycin were transferred to intensive care and none died."
Thanks to Mahevas et al for clarifying their data. The results for the HCQ + AZ dual therapy are spectacular.
"None of the 15 patients who received a combination of hydroxychloroquine and azithromycin was transferred to intensive care and none died." https://t.co/NvNNs65Rhw pic.twitter.com/euK5wr6hOI
These arguments can also backfire on the work carried out by Professor Raoult himself. “Consider, like Professor Raoult, that it is at the very beginning of the disease that the drug must be given for it to have an effect. As we know that there will be no evolution towards serious forms for 85% of the patients, that means that it is necessary to include a lot of patients to be able to demonstrate a possible positive effect ", judge Olivier Bouchaud.
“Pr Raoult's team took the scientific approach backwards, starting from the premise that the treatment works. We have had a plethora of poor quality studies, with only observational studies, starting with those carried out in Marseille ”, asserts Professor Mathieu Molimard, head of the medical pharmacology service at the Bordeaux University Hospital.
Will we ever know definitively if hydroxychloroquine is effective?
Several criteria must be met for a study to be methodologically indisputable: that it includes a control group receiving nothing or a placebo, that it is randomized (that is to say that the patients are randomly placed in a group or the other), and that it was published in a medical journal. Which requires… time.
Several large clinical trials have been launched. One of them, baptized PrEP Covid, will allow us to examine the possible benefit of hydroxychloroquine as a preventative for caregivers. 900 volunteers have been recruited since mid-April and divided into three groups (one taking hydroxychloroquine, the other taking azithromycin, and the last a placebo). But the results are not expected before the end of June, at the earliest.
There are also hopes for the European Discovery trial. Contrary to what was initially planned, this includes hydroxychloroquine (alone) among the five molecules tested. But the results will come very late, due to the difficulty in recruiting enough patients in several European countries.
However, the health crisis that the world has experienced since the start of the year is so severe that many would prefer not to have to wait. And there will always be people left to challenge or maintain their opinion. This makes Pr Lelièvre fear that we "never manage to answer definitively". “There was such confusion from the start on this molecule that we will never manage to return to a scientific and rigorous discourse. The damage is done, ”he concludes.