July 31, 2020

expert reaction to living systematic review on remdesivir in hospitalised severe COVID-19 patients

A study, published in the BMJ, looked at remdesivir in hospitalised severe COVID-19 patients.

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

“This “Rapid Recommendation” on remdesivir in patients with severe Covid-19 is to be welcomed.  Its cautious approach is entirely justified.  The review suggests that the evidence for benefit is largely in terms of time to clinical improvement and that uncertainty remains over benefit in mortality.

“They note that current evidence suggests there are no serious adverse reactions caused by remdesivir that we know about, but the limited numbers studied and the limited follow-up mean that rare but very serious adverse reactions may not have been detected yet.  The evidence from trials in which remdesivir only was used give some reassurance on this as well, but it is important for those who use the drug to be aware of the limitations of current experience with remdesivir.  It is not a drug with dramatic benefits, but in the longer term it might be seen as one which, if combined with other, as yet unknown drugs, could give useful efficacy.

“Although the authors of these guidelines note that the two trials on which they base the guideline required the drug to be given within 12 days of symptom onset, they do not emhasise this limitation in the guideline.  They note that one of the trials suggested that remdesivir given within 10 days of symptom onset was more effective than giving it at later times.  While this is weak evidence as a post-hoc observation, it does suggest that the use of the drug may be quite limited in practice.  To require it to be given within 10 days of symptom onset but also to have severe disease is certainly targeting a group where such benefit is important, but we do not know what proportion of patients meet that requirement.  There will be a temptation to use it outside these restrictions and it may well have reduced or even little efficacy in those with say mild or moderate Covid-19 or those severe patients whose first symptoms were 12 or more days previously.

“Its practical impact may also be affected by the need for intravenous administration, its high cost and possibly limited availability.  Dexamethasone works at a later stage of severe disease, is very low cost and easy to administer, so if there is doubt over the time since first symptoms in patients with severe disease, dexamethasone may be preferred.  It also has limitations in terms of the spectrum of patients for whom there is demonstrated benefit.”

‘Remdesivir for severe covid-19: a clinical practice guideline’ by Bram Rochwerg et al. was published in the BMJ at 00:01 UK time on Friday 31 July 2020.

DOI: 10.1136/bmj.m2924

Declared interests

Prof Stephen Evans: “No conflicts of interest in relation to this.  I am funded (1 day/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 or any grants obtained from them.  I am the statistician to the “meta-Data Safety and Monitoring Board” for CEPI.  I will probably be paid for my attendance at meetings and expenses for travel.”