February 11, 2021

expert reaction to the RECOVERY trial reporting that tocilizumab reduces deaths in patients hospitalised with COVID-19

The results of the tocilizumab arm of the RECOVERY trial have been announced.

This Roundup accompanied an SMC Briefing.

Dr Nick Cammack, COVID-19 Therapeutics Accelerator Lead at Wellcome, said:

“These results are highly promising and testament to the incredible scientific effort from the RECOVERY trial. Saving one life in every 25 patients treated with tocilizumab would have a significant impact on mortality and alleviate pressure on overstretched healthcare systems.

“Tocilizumab is a monoclonal antibody, which is already used as an arthritis medicine. This class of treatments – which also includes medicines for cancer and autoimmune diseases – is traditionally one of the most expensive and inaccessible in the world, and notoriously difficult for patients in low- and middle-income countries to access.

“As these results show, monoclonal antibodies are among the most promising treatments for COVID-19. This includes the new and combination monoclonal antibodies that are specific to COVID-19. The pandemic must be the catalyst to finally make these transformative treatments affordable and accessible to everyone globally.

“As hospitalisations and deaths from COVID-19 surge across the world and the new strains make the pandemic more challenging, finding effective treatments is more urgent than ever. We need treatments that work across all stages of the disease – from mild to severe. We must keep up the rapid pace of research, continuing to invest in large-scale clinical trials like RECOVERY that can provide the world with definitive answers.”

Prof Robin Ferner, Honorary Professor of Clinical Pharmacology, University of Birmingham & Honorary Consultant Physician, City Hospital Birmingham, said:

“At last we have good evidence from a randomised trial in over 4000 patients with COVID-19 that tocilizumab does save lives – at least if the peer-reviewed data when published bear out the summary findings from RECOVERY put out today. The results also show that the drug reduces the chance of patients who need oxygen treatment deteriorating to the extent that they need mechanical ventilation – and that will ease the burden on intensive care units.

“The benefit from tocilizumab comes in addition to the benefit from dexamethasone – the steroid increases the chance of recovery in severe COVID disease. Unlike dexamethasone, tocilizumab is expensive, but it could save one life for every 25 treated COVID patients. Another excellent result for research sponsored by and conducted in the NHS by the Oxford research group.”

Prof Duncan Richards, CLIMAX Professor of Clinical Therapeutics, University of Oxford, said:

“There have been a relatively large number of small and medium studies with tocilizumab showing mixed results, and to date there has been an ongoing debate on the role of this drug in COVID-19. The RECOVERY trial highlights the value of large simple studies to provide definitive information on treatments that have shown promise in smaller studies. It is encouraging to see that there is an incremental effect over and above that from dexamethasone.

“These data are important, but the search for effective treatments must continue as intravenous monoclonal antibody treatments such as tocilizumab will not be available to all patients worldwide.”

Prof Athimalaipet Ramanan, Professor of Paediatric Rheumatology, University of Bristol, said:

“The RECOVERY trial has highlighted what the ‘need of the hour’ is – clear evidence on the role of tocilizumab. Currently, the evidence from small clinical trials has been equivocal on the role of tocilizumab. However, RECOVERY and REMAP-CAP clearly demonstrate that tocilizumab does have a significant impact on reducing mortality in those with COVID-19 requiring oxygen or being ventilated.

“After dexamethasone (steroids), this is the most significant advance in the treatment of COVID that has an impact in reducing deaths.

“RECOVERY has clearly shown the importance of doing large clinical trials to address key questions. One of the reasons why some of the other trials failed to show this effect could well be the smaller number of patients recruited in those studies.”

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

“This randomised controlled trial platform has already shown convincing results both in terms of efficacy (e.g. dexamethasone) and lack of efficacy (e.g. hydroxychloroquine). These new results are very encouraging, not only because they show benefit for the arthritis drug tocilizumab, but because most (82%) of the patients in the treated and the control arms were receiving dexamethasone. The evidence on efficacy of dexamethasone became known after recruitment to this trial had begun, and so the efficacy of tocilizumab is in addition to that of dexamethasone.

“It is not a treatment intended for early or preventive use, but for very ill patients in hospital with COVID-19 who required oxygen and had evidence of inflammation. It is a large trial and the benefits were seen both on earlier discharge from hospital and mortality, at 28 days after starting treatment.

“The magnitude of benefit is not startling but is clinically important, with a reduction in deaths from 33% to 29%. The large size of the trial, and the careful way this trial has been conducted, lends confidence to this assertion of benefit in patients who are very ill.”

Prof Anthony Gordon, Professor of Anaesthesia and Critical Care and NIHR Research Professor, Imperial College London, said:

“These are exciting results and fully support the earlier results from REMAP-CAP, that tocilizumab improves survival in seriously ill patients with COVID-19. The REMAP-CAP trial demonstrated that this drug was useful for critically ill patients in intensive care and provided additional benefit when given with steroids. The new data from the RECOVERY trial have independently confirmed this result and also shown there is benefit for less severely ill patients in general wards in the hospital.

“This is great news. We know approximately 4,000 critically ill patients have already been treated with tocilizumab in the UK since the REMAP-CAP result was announced. Now even more patients will benefit from this treatment.

“The fact that these two large trials have been led from the UK also shows the power of the National Institute for Health Research (NIHR) to deliver world-leading clinical trials within the NHS to tackle this global pandemic.”

Preprint: https://www.medrxiv.org/content/10.1101/2021.02.11.21249258v1

Press Release: https://www.recoverytrial.net/news/tocilizumab-reduces-deaths-in-patients-hospitalised-with-covid-19

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

www.sciencemediacentre.org/tag/COVID-19

Declared interests

Dr Nick Cammack: “The RECOVERY Trial receives core funding from a number of funders, including Wellcome.”

Prof Athimalaipet Ramanan: “Prof Ramanan was part of the steering committee of a trial of tocilizumab in India which is due to be published soon, and is part of the RECOVERY paediatric steering group. He has also acted as a consultant for Roche.”

Prof Stephen Evans: “No conflicts of interest. I am funded (one day per week) by LSHTM. They get funding from various companies, including AstraZeneca 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/AstraZeneca trial, and on 13th January 2021 learnt I had received the active vaccine.”

Prof Anthony Gordon: “Anthony Gordon is the UK Chief Investigator for the REMAP-CAP trial (funded by NIHR and EU FP7 grants, with contribution of drug supplies from Roche, Sanofi and SOBI). His salary is supported through an NIHR Research Professor award and from the NIHR Imperial Biomedical Research Centre, as the Chair of Anaesthesia & Critical Care at Imperial College London and he works as a consultant in Intensive Care at Imperial College Healthcare NHS Trust. He has received consulting fees in the past three years from GSK, Bristol Myers Squibb and 30 Technology with fees paid to his institution. He has a current collaborative research grant from EIT Health with bioMérieux.”

None others received.