Samedi 13 juin 2020. Chronique de l'hydroxychloroquine. Acte 7. Le vent tourne dans la littérature...

Certains de mes proches me font remarquer avec tristesse (semble-t-il) que je n’ai pas publié de billet depuis lundi dernier. C’est que j’ai par ailleurs beaucoup de travail. Tout de même, je me suis penché sur la littérature relative au traitement de la Covid-19 ; elle est en train d’exploser. Je note tout de même un changement de ton dans la manière d’envisager la question. La plupart des articles d’intérêt sont des méta-analyses des résultats observationnels et des essais cliniques publiés (SINGH et al. ; GBINIGIE and FRIE K.). Ils se prêtent donc à la critique de ce type de travail. Néanmoins, ils donnent une vue nettement plus nuancée (LITTLEJOHN) que celle claironnée dans le Lancet.

Tous les auteurs ou presque commencent par dire avec une sorte de pudique et touchante unanimité qu’il n’y a aucun traitement qui se soit montré efficace lors d’essais cliniques randomisés en double aveugle et que tout de même, bon, en fait, ce serait bien d’en faire avec l’hydroxychloroquine, pour essayer, quoi (Voir MACK). Quand on a un peu l’habitude de lire la littérature scientifique, on voit ce que cela signifie vraiment. Il est tout à fait symptomatique de constater que les Indiens (SINGH et al.) ne s’embarrassent pas de vaines précautions et recommandent l’usage de l’hydroxychloroquine pour le traitement de la Covid-9. Plus important encore est l'analyse faite par SHITTU et AFOLAMI, de l’Université du Michigan, qui indique que l’adjonction de zinc au traitement en augmente l’efficacité dont, eux, ne doutent pas. Il s’agit d’une étude théorique et non clinique

J’écoutais ce matin le cours d’épistémologie de Didier RAOULT. Il faisait allusion à de grands chercheurs en théorie des sciences (POPPER, KUHN, FEYERABEND) et à un autre dont j’ai oublié le nom. Le recours obligatoire à l’essai clinique randomisé en double aveugle relève de la croyance et non de la science, dit-il. Et en effet, il s’agit d’une « méthode » qui stérilise l’imagination et nie la valeur de l’observation, de l’empirisme et de ce que les anglais appellent la serendipity.

Voici une liste de quelques articles. Je les commente quand cela est nécessaire.

A. K. SINGH, A. SINGH, A. SHAIKH, R. SINGH, A. MISRA

Chloroquine and hydroxychloroquine in the treatment of COVID-19 with or without diabetes: A systematic search and a narrative review with a special reference to India and other developing countries

Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 14, 2020, 241e246.

Background and aims: No drugs are currently approved for Coronavirus Disease-2019 (COVID-19), although some have been tried. In view of recent studies and discussion on chloroquine and hydroxychloroquine (HCQ), we aimed to review existing literature and relevant websites regarding these drugs and COVID-19, adverse effects related to drugs, and related guidelines. Aims and methods: We systematically searched the PubMed database up till March 21, 2020 and retrieved all the articles published on chloroquine and HCQ and COVID-19. Results: Two small human studies have been conducted with both these drugs in COVID-19, and have shown significant improvement in some parameters in patients with COVID-19.

Conclusion: Considering minimal risk upon use, a long experience of use in other diseases, cost effectiveness and easy availability across India, we propose that both these drugs are worthy of fast track clinical trial for treatment, and may be carefully considered for clinical use as experimental drugs. Since HCQ has been approved for treatment of diabetes in India, it should be further researched in diabetes and COVID-19, a subgroup where significant mortality has been shown.

(Voici un extrait de la conclusion :

Although evidence of chloroquine and HCQ is limited (based on the experimental data and only two small human trials), consideringthe potentially favorable benefit-risk balance of chloroquine and HCQ in absence of any other valid treatment option, we believethat such treatment could be useful in the current context ofpandemic COVID-19 outbreak. We have summarized current consideration and proposed line of management in Table 3. The lowcost of chloroquine and HCQ could also be an effective strategy to counter COVID-19 (especially in patients with diabetes and other co-morbidities in whom mortality is high) in resource constrained and COVID-19 overburdened heath care systems in middle- and low-income counties including India.

MACK HG.

Hydroxychloroquine use during the COVID-19 pandemic 2020.

Aust J Gen Pract. 2020 Apr 14;49. doi: 10.31128/AJGP-COVID-08. Online ahead of print.PMID: 32294807

At present, there are no studies demonstrating the clinical efficacy of hydroxychloroquine for the prophylaxis or treatment of COVID-19 infection....

D'où la nécessité d'essais randomisés.

LITTLEJOHN E.C.

Hydroxychloroquine use in the COVID-19 patient.

Clin J Med. 2020 May 5.

Abstract

Hydroxychloroquine (HCQ) has multiple potential antiviral mechanisms of action that differ according to the pathogen studied (eg, Chikungunya, Dengue virus, human immunodeficiency virus, poliovirus, Zika virus). Data on HCQ for treatment of coronavirus disease 2019 (COVID-19) are rapidly evolving. To date there is no evidence from randomized controlled trials that any single therapy improves outcomes in patients infected with COVID-19. There are also no clinical trial data supporting prophylactic HCQ therapy in COVID-19. Hydroxychloroquine (HCQ) use in patients with COVID-19 is being investigated examining prophylaxis, postexposure prophylaxis, and treatment regimens.…

Il faut revoir votre bibliographie, Emily...

GBINIGIE K, FRIE K.

Should chloroquine and hydroxychloroquine be used to treat COVID-19? A rapid review.

BJGP Open. 2020 Apr 7:bjgpopen20X101069.

doi: 10.3399/bjgpopen20X101069. Online ahead of print.PMID: 32265182

BACKGROUND: On the 11 March 2020, the World Health Organization (WHO) declared that COVID-19 was a pandemic.

Abstract

Background: On the 11 March 2020, the World Health Organization (WHO) declared that COVID-19 was a pandemic. To date, there are no medical treatments for COVID-19 with proven effectiveness. Novel treatments and/or vaccines will take time to be developed and distributed to patients. In light of this, there has been growing interest in the use of existing medications, such as chloroquine (CQ) and hydroxychloroquine (HCQ), as potential treatments of this disease.

Aim: To establish the current evidence for the effectiveness of CQ and HCQ in treating COVID-19.

Design & setting: A rapid review of the literature was conducted.

Method: Electronic searches in PubMed and Google Scholar were conducted on 21 March 2020. A further search was conducted in Google for relevant literature on 28 March 2020.

Results: There is limited evidence of in vitro activity of CQ/HCQ against SARS-CoV-2. A number of in vivo clinical trials are underway. The empirical data available from two of these trials reveal conflicting results. Both trials are characterised by small numbers of participants (n = 30 and n = 36) and suffer methodological limitations. No medium or long-term follow-up data is available.

Conclusion: At present, there is insufficient evidence to determine whether CQ/HCQ are safe and effective treatments for COVID-19. High quality, adequately powered randomised clinical trials in primary and secondary care settings are urgently required to guide policymakers and clinicians. These studies should report medium- and long-term follow-up results, and safety data.

C’est faux, ou alors les auteurs font mal leur bibliographie. L’équipe marseillaise a publié sur une série de plus de 1000 patients. Elle a soumis au Lancet (qui l’a refusé) ses observations portant sur plus de 3000 patients… Ne parlons pas de la série de DAVIDO qui a été accessible sur MedRxiv et a été retirée pour éviter d’ajouter de la polémique à la polémique, mais porte sur plus de 150 patients. J’ai été en correspondance avec DAVIDO (équipe du Pr PERRONNE) en lui faisant savoir que je regrettais ce retrait (non pas qu’il retire l’article, mais il le soumet directement sans passer par MedRxiv). Les résultats sont spectaculaires. L’article est soumis. Nous verrons bien s’il paraît. 
PS. Je viens de voir la critique très argumentée de Julien HERNANDEZ sur cette étude. Mais HERNANDEZ adopte le point de vue des algorithmiques. La question qui se pose ici est la suivante : mauvaise statistique ou non, les gens traités par l'hydroxychloroquine ont-ils mieux traversé la maladie que les non traités. Les résultats de DAVIDO disent : oui !

M. O. SHITTU, O. I. AFOLAMI.

Improving the efficacy of chloroquine and hydroxychloroquine against SARS-CoV-2 may require zinc additives - A better synergy for future COVID-19 clinical trials

Le Infezioni in Medicina, n. 2, 192-197, 2020

Biological Science Department, Michigan Technological University, Houghton, Michigan, United States of America

The recent outbreak of coronavirus disease 2019 (COVID-19), has now been officially declared as a pandemic by the World Health Organization. As of now, there is no known effective pharmaceutical agent against the SARS-CoV-2 virus. However, several precautionary measures have been prescribed to prevent further spread of the virus, which include avoidance of social gatherings, proper handwashing, frequently disinfecting of used items and surfaces and so on. More recent studies have highlighted the possibility of treating patients infected with the novel SARS-CoV-2 virus with chloroquine and hydroxychloroquine, of which mechanism of action is not completely understood. We seek to draw the attention of the scientific community to the possibility of drastically reducing the effects of the virus on the affected patients and improving clinical trials outcome through the synergistic action of zinc and chloroquine in patients suffering from the coronavirus disease.

Le vent tourne mes amis, le vent tourne. La vérité finira bien par sortir toute nue du puits. Et enfin la médecine sera pilotée par des cliniciens et non par des algorithmes.