Paris (AFP)
Brazil generalizes its use, Donald Trump takes it every day, but a new study evokes increased risks of death: what do we know about the very controversial hydroxychloroquine - derivative of the antimalarial chloroquine - currently tested in several countries against Covid -19?
What is that?
Chloroquine has been prescribed for several decades against malaria, a parasite carried by the mosquito.
Its derivative, better tolerated, hydroxychloroquine (HCQ), known in France under the name of Plaquénil, is prescribed against lupus or rheumatoid arthritis. Most often, the HCQ is tested against the Covid-19.
These molecules, known and inexpensive, have raised a lot of hope, especially in Africa.
But they are far from being the only ones to be tested: more than 800 clinical trials seek to evaluate dozens of potential treatments, according to the medical journal The Lancet.
Hydroxychloroquine has known unprecedented fame since the end of February since Pr Didier Raoult, from the Institut hospitalo-universitaire (IHU) Méditerranée-Infection, in Marseille, relayed a small, little detailed Chinese study, claiming that chloroquine phosphate showed signs of efficacy in patients with SARS-CoV2.
The excitement around hydroxychloroquine then gained momentum when US President Donald Trump made himself its apostle, to the point of taking it daily as a preventive measure.
In Brazil, President Jair Bolsonaro is convinced of its effects, yet unproven, to the point that the Ministry of Health on Wednesday recommended its use for all patients with mild illness.
Going far beyond the political realm, hydroxychloroquine has become a subject of much publicized public and political debate, sparking heated discussions in the family and in the media, and fierce outbursts on social networks.
Is hydroxychloroquine effective against Covid-19?
That's the whole question.
The hypothesis of an action of these molecules against the new coronavirus comes from the fact that their antiviral properties have shown in vitro or on animals and on different viruses, sometimes positive results.
Studies have also shown in vitro effects on SARS-Cov2 but very often, scientific results in vitro are not found in vivo in humans.
As for efficacy on humans against SARS-Cov2, there is no scientific consensus, due to the lack of sufficient experience and studies conducted according to the usual rules: randomization (patients chosen by lot ), "control group" (patients receive treatment, others do not), "double-blind" (patients and doctors do not know who took the treatment and who received the placebo).
Most of these studies are, moreover, carried out on a limited number of patients.
Finally, a study must be published in a scientific journal after critical review and validation by other scientists, independent of those who conducted the tests.
To date, there are no studies that meet all these criteria at the same time and many contain methodological biases, more or less significant.
Professor Didier Raoult has released several studies, which he says show the effectiveness of hydroxychloroquine combined with an antibiotic, azithromycin. For him, the health emergency justifies that we widely give this drug.
He advocates the administration of this dual therapy at the first symptoms and claims in his third study on more than 1,000 patients that after 10 days, more than nine in ten (91.7%) no longer had a viral load.
But this figure, like that of the mortality of treated patients, is comparable to that observed in the event of natural progression of the disease.
Among the methodological biases of this study, pointed out by other scientists: no control group, which prevents demonstrating anything about the effectiveness of HCQ.
In addition, 95% of the treated patients showed no signs of severity. Like most patients, they could therefore have healed spontaneously.
A study carried out in New York hospitals and published at the beginning of the month in the American journal NEJM shows that hydroxychloroquine has neither improved nor significantly deteriorated the situation of patients in serious condition.
Two studies, one Chinese and one French, published last week, find that the HCQ does not significantly reduce the risks of admission to intensive care or death in patients hospitalized with pneumonia due to Covid-19.
And another study, with data on a total of 96,000 patients, published in The Lancet on Friday, concludes that neither chloroquine nor HCQ are effective against Covid-19 in hospitalized patients, and that these molecules even increase the risk of death and arrhythmia.
It is the "first large-scale study" to show "robust statistical evidence" that these treatments "do not benefit patients of Covid-19," said lead author Dr Mandeep Mehra.
The risks
Choloroquine especially but also hydroxychloroquine are drugs whose side effects can be significant, even serious.
The French drug agency ANSM particularly warned of the cardiac risks linked to the combination of HCQ and azithromycin.
The Swedish Medicines Agency banned the prescription of chloroquine and hydroxychloroquine on Covid-19 on April 2 for lack of sufficient safety data.
Because knowledge is too limited, the European Medicines Agency, in particular, believes that these medicines should "only be used for clinical trials or emergency programs" within the framework of strict protocols validated in each country.
Similarly, the study published on May 22 in The Lancet recommends limiting these treatments to clinical trials.
Who uses it and in what context?
These molecules - generally HCQ, more rarely chloroquine - are administered to Covid-19 patients in many countries.
But the framework is often limited: clinical trials and in general in the hospital. Sometimes only for severe cases, sometimes for the least affected.
A notable exception since Wednesday: the Brazilian Ministry of Health recommended the use of chloroquine and hydroxychloroquine for patients slightly affected by Covid-19.
However, "as there are no complete studies proving the benefits of these molecules for the treatment of Covid-19, (...) the decision to prescribe them rests with the doctor, with the patient's agreement", adds the ministry.
In the United States, the drug agency (FDA) has authorized use, but only in hospital "appropriately, when a clinical trial is not available or feasible". And not as a precaution, as Donald Trump boasted.
Apart from clinical trials, France has restricted the use of hydroxychloroquine in hospitals only and only for serious cases on the collegial decision of doctors.
In Senegal, many patients with coronavirus have received hydroxychloroquine in hospitals. It is also used in Chad, Syria, Algeria, Morocco ...
In Russia, it is also distributed to hospitals to treat patients who test positive or suspected of being infected.
In terms of clinical trials: the Angers and Bordeaux teaching hospitals are testing hydroxychloroquine, while a study carried out on 900 caregivers must assess whether hydroxychloroquine and azithromycin are effective in prevention.
The European trial (Discovery) which is testing four treatments including hydroxycholoroquine and which raised a lot of hope is proving more complicated than expected, especially due to the lack of patients. He will probably not deliver conclusions for several weeks.
In any event, despite the high hopes, we should not expect any "miracle molecule". Otherwise, researchers who started trials earlier, in China and Italy, "would have already found it," warned Professor Florence Ader, who is piloting the Discovery study, on May 7.
© 2020 AFP