July 28, 2021

expert reaction to Cochrane review on ivermectin for preventing and treating COVID-19

A review, published in the Cochrane Database of Systematic Reviews, looks at the use of Ivermectin for preventing and treating COVID‐19.

Dr Penny Ward, Faculty of Pharmaceutical Medicine, Visiting Professor in Pharmaceutical Medicine, Kings College London, said:

“This timely review by the Cochrane collaborative group confirms the lack of sufficient clinical evidence supporting the assertion of benefit from use of ivermectin for the treatment or prevention of COVID. The authors have provided an exhaustive summary of the available evidence, which demonstrates the sub optimal design and reporting of many studies, as well as a summary of ongoing work, which may be anticipated to define the utility of the agent more precisely. It should be noted that the initial screening in vitro data suggested antiviral effects for this agent require high concentrations of the agent in target tissues. However, doses used in trials to date were too low to achieve these concentrations, suggesting that doses considerably higher than those being used in the ongoing clinical trials may be needed. This might require alternative formulations to improve oral bioavailability or direct pulmonary administration via inhalation which might increase the potential for efficacy while reducing potential toxicity. Higher doses/systemic exposure will require additional safety evaluation, given the toxicity of the product to liver and kidney. In the meantime, clinicians should not be using ivermectin for the treatment or prevention of COVID in practice. In addition, clinicians responsible for the studies that are ongoing might perhaps consider early evaluation of outcomes for futility.”

Prof Stephen Evans, Professor of Pharmacoepidemiology, London School of Hygiene & Tropical Medicine, said:

“This is a good review from experienced reviewers.  They are transparent about which studies are included and which are included.  They apply sensible criteria for both of these.

“Their overall conclusion that any benefit to ivermectin in prevention or treatment was at best uncertain.  There was no clear evidence of harm.  Their conclusions are in contrast to some other reviews that were not done as carefully and which included trials of doubtful validity.  Any benefit at any stage of the disease process from infection to prevention of death will require large carefully-conducted randomised trials.  Such trials are under way now.

“This review confirms previously issued advice from WHO, EMA and FDA that ivermectin should only be used in the context of a randomised trial and should not be used for routine treatment or prevention of Covid-19.”

Dr Stephen Griffin, Associate Professor in the School of Medicine, University of Leeds, said:

“This Cochrane review supports the consensus that reported successes attributed to poorly designed RCTs or off-label use of Ivermectin, are both unfounded and unreliable.  Recent concerning revelations around some of the most highly cited Ivermectin studies add to this claim, and undermine meta-analyses upon which they are based.  Whilst the outcome of the Solidarity trial should be awaited to confirm, it seems highly unlikely that this drug can, or should be repurposed to treat SARS-CoV2 infection.  Continuing its off-label use should therefore be considered unacceptable at the present time.”

‘Ivermectin for preventing and treating COVID‐19’ by Maria Popp et al. was published in the Cochrane Database of Systematic Reviews on Wednesday 28 July 2021.

DOI: 10.1002/14651858.CD015017.pub2

https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD015017.pub2/full

All our previous output on this subject can be seen at this weblink:

www.sciencemediacentre.org/tag/covid-19

Declared interests

Dr Penny Ward: “No COIs. I am semi-retired, but I am owner/Director of PWG Consulting (Biopharma) Ltd a consulting firm advising companies on drug and device development.  Until July 2019 I was Chief Medical Officer of Virion Biotherapeutics, which was a company developing broad spectrum RNA therapy for the treatment/prevention of respiratory virus infections.  Between December 2016 and July 2019 I served as Chief Medical Officer of Virion Biotherapeutics Ltd, a company developing antiviral treatments for respiratory viral diseases.  Previous employee of Roche, makers of tocilizumab (anti IL6 antibody) and CMO of Novimmune, makers of empalumab (anti IFN gamma antibody).”

Prof Stephen Evans: “No conflicts of interest.  I am funded (one day per week) by LSHTM.  They get funding from various companies, including Astra Zeneca and GSK but I am not funded by them, I have no involvement in obtaining funding from them and I am not an investigator on any grants obtained from them.  I am the statistician to the ‘meta-Data Safety and Monitoring Board’ for CEPI.  I am paid for my attendance at those meetings and will be paid expenses for travel if that occurs.  I am a participant in the Oxford/Astra Zeneca trial, and on 13th January 2021 learnt I had received the active vaccine.”

Dr Stephen Griffin: “No conflicts.”