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On the safety of combined hydroxychloroquine and azithromycin treatment
Again, numerous comments and articles in the mainstream media have suggested that this treatment could be dangerous, and we have been witnessing for several weeks
a flood of untruths on this subject in the media (
23 )
Yet there is ample evidence that all of this is wrong.
As many people know, hydroxychloroquine has long been prescribed for malaria and has been used for decades in the majority of patients with Lupus Erythematosus and Rheumatoid Arthritis in doses ranging from 200 to 600mg per day . These treatments are taken by patients over long periods (up to several years). The serious side effects mentioned are rare cases of heart and ophthalmic problems.
In addition, recent figures from the ANSM show that between 2017 and 2019, out of almost 4 million boxes of Plaquenil (Hydroxychloroquine) sold, only 2 deaths have been reported, including one case in the context of drug intoxication in a subject taking 6 psychotropics in addition to hydroxychloroquine. (
24 )
As early as March 29,
the American College of Cardiology made it clear that on the one hand several hundred million chloroquine treatments had been used worldwide - making it one of the most widely used drugs in history - without any report of arrhythmic death under the supervision of the WHO and that, on the other hand, in vivo studies had shown no arrhythmic synergistic effect of azithromycin with or without chloroquine (
25 ).
More specifically, studies have been done on the safety of the combination of hydroxychloroquine and azithromycin in patients with Covid19. In both studies, it was concluded that this treatment was not associated with excess mortality, deploring no "torsade de point" and some cases of QTc prolongation that a simple cessation of treatment resolved. (
26 ,
27 )
So contrary to what circulates on both sides, with medical monitoring, this treatment does not present a risk.
And finally what say the publications which conclude that it is not effective
Recently,
the general press highlighted two articles published in the famous
British Medical Journal , a Chinese study (
31 ) and a French study (
32 ) which concluded that hydroxychloroquine was ineffective. However, these two studies show many biases, never mentioned in the press.
In the study by Tang
et al. (
31 ), the main biases are that in the group with hydroxychloroquine (HCQ) the patients were older, had more comorbidities, and had received almost twice as much HCQ as those recommended. The majority of patients in the groups (including the controls) had also received antivirals (which is annoying to measure the antiviral effect of HCQ versus the control group). The mean duration before treatment was 17 days (far too long for antiviral therapy). Despite these biases, the study shows a positive effect of 4 points *** between the HCQ group and the control group.
However, the authors prefer to conclude that there is no efficacy of HCQ .
In the study by Mahévas
et al. (
32), the patients were all in a severe condition (severe acute respiratory syndrome with need for oxygen). Curiously in the control group, 29% of the patients also took azithromycin, while only 18% of the cases took it in the HCQ group. When looking at patients transferred to intensive care (ICU), the HCQ effect is nevertheless visible since 1.5 times less ICU transfer in the HCQ group is observed compared to the control group. But above all, in an extraordinary way, we can see in the details of the study that in the small group of patients taking both HCQ and azithromycin, there were zero deaths and no transfer to ICU. On the other hand, the small control group also taking azithromycin (but no HCQ) had to deplore 6 ICU admissions and 5 deaths.However, the authors also prefer to conclude that hydroxychloroquine is ineffective while
the study clearly shows the efficacy of the hydroxychloroquine + azithromycin treatment versus the control taking only azithromycin.
Then in the New York study by Rosenberg
et al. (
33 ), not only the hydroxychloroquine (HCQ) patients - supplemented or not with azithromycin (AZT) - are much older, obese and diabetic than the control group (these are major risk factors for mortality under Covid19) but also plus the HCQ + AZT group has very significantly low oxygen saturation, which is again a major factor in predicting mortality in this disease (
34). As a result, many more patients in the HCQ +/- AZT groups (in 95 to 82% of cases) have abnormal lung X-rays versus the control group (in 55% of cases only). In this study, it is therefore compared groups of older patients, more obese, more diabetic and much more advanced in the disease against a control group where the patients are less at risk and are less advanced in the disease.
This does not make sense and it is very open to criticism in a study of this type .
Another retrospective New York study by Geleris et al (
35 ), show the same biases as the previous one, of patients in the older HCQ group who were mostly already in mild to moderate acute respiratory distress syndrome (ARDS) at the time. that the patients in the control group were not. Yu
et al. also point out that in this study the initial dose of HCQ given to these very sick patients was far too high (1200mg on day 1), while this Chinese team had very good results with 400mg / day (
17). But the most interesting in this study is that the "End-point", that is to say the criterion of evaluation of the effectiveness or not of the treatment, was "intubation OR dead" which is already curious at the base , (it is still very different to be intubated or to be dead). By looking in detail at the deceased and intubated patients, everything changes. The study shows that COVID patients who have developed respiratory distress survive much more when they are treated with HCQ versus the control group (data that can only be found in the study annexes).
Nevertheless, the authors forget to raise this point from their study.
Finally, the famous American study on veterans (
36 ), the Marseille IHU published a response on this subject as this study shows bias in the differences of the groups studied (
37 ). The groups treated with HCQ + / - AZT (with doses which are never specified in the article) consisted on average of 30% of “dying” patients versus the control group (only 14%) to whom they presumably given the treatment in desperation. In addition, a third of patients in the control group also took azithromycin.