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The REMAP-CAP trial has reported that critically ill COVID-19 patients treated with tocilizumab are more likely to have improved outcomes.
This Roundup accompanied an SMC Briefing.
Prof Martin Landray, Professor of Medicine & Epidemiology, Nuffield Department of Population Health, University of Oxford, said:
“It is always nice to receive encouraging news, particularly as we are at such a challenging stage of the epidemic. But we should not get carried away. Several previous trials of this drug (of similar size) have produced mixed results.
“The current report lacks important detail about the levels of respiratory support these patients were receiving, how many were also treated with dexamethasone or other corticosteroids, the duration of stay in the intensive care unit or in the hospital, and on how many patients died.
“Consequently there are important outstanding questions:
– Does tocilizumab impact survival, duration of ICU stay, or both – and to what extent?
– Does tocilizumab work on top of steroids?
– Does tocilizumab work in the many more patients who are not on ICU?
“Hopefully some of these questions will be answered in the full report. But I suspect that it will need a much larger body of evidence from randomised trials to provide clear-cut answers to all of these important questions.”
Prof Athimalaipet Ramanan, Honorary Professor of Paediatric Rheumatology, University of Bristol, said:
“The REMAP-CAP study results as per press release is of significant interest. We will need to see the full data to draw firm conclusions.
“Two recent RCT’s (including one published in NEJM) did not show a benefit for patients treated with Tocilizumab. However, there was another trial published in JAMA recently which did show efficacy.
“It is likely that Tocilizumab will benefit some patients. What is still not clear is how we identify the patient population with COVID-19 which is likely to benefit from Tocilizumab.”
Prof Stephen Evans, Professor of Pharmacoepidemiology, London School of Hygiene & Tropical Medicine, said:
“One of the recent trials reported in the NEJM (https://www.nejm.org/doi/full/10.1056/NEJMoa2028836) in hospitalised patients did not find a survival benefit for those taking tocilizumab. Such patients are less severely ill than those reported in the REMAP-CAP trial. The size of the beneficial effect reported in this trial does not appear that high and combines survival with need for intense support. Therefore I think these results need to be treated with caution at this early stage.
“Perhaps combining the data from all the reported trials would suggest there is benefit of taking tocilizumab when severely ill with COVID-19 but it may not be large. However it is possible that different drugs work best at different times during illness with Covid. It seems remdesivir may well work early in the disease process (and not at later stages) while dexamethasone works well at later periods (and not in earlier stages of the disease). The most relevant comparator for tocilizumab should therefore be dexamethasone. Does dexamethasone or tocilizumab provide greater benefit, or are there particular patients benefitting from one but not the other, and what are the cost implications?”
Prof Athimalaipet Ramanan, Honorary Professor of Paediatric Rheumatology, University of Bristol, said:
“Based on limited data shown (all we have is a press release) it is hard to make any conclusions.
“Tocilizumab has not been shown to be effective in 2 RCT’s (Stone el al in NEJM and COVACTA study by Roche) and possibly of benefit in another RCT.
“Whilst promising, we need see the full manuscript of today’s results to make any firm opinion.
“Tocilizumab may be of benefit to certain patients with COVID-19, the difficulty appears to be in identifying this patient group.
“RECOVERY trial’s data on Tocilizumab is yet to be published. The key difference between the 2 studies (RECOVERY and REMAP-CAP) is that REMAP-CAP recruits more severely ill patient (about to be ventilated or ventilated).”
Prof Peter Horby, Professor of Emerging Infectious Diseases and Global Health in the Nuffield Department of Medicine, University of Oxford, said:
“Results on the use of steroids in severe COVID have provided proof of principle that anti-inflammatory drug can help, so this is an encouraging result which suggests that other, more targeted, anti-inflammatory drugs may also help.
“The results so far on tocilizumab have been mixed, with four randomised controlled trials having reported results, of which two were negative and two were positive. None have reported a mortality benefit at day 28 or 30. The results from REMAP-CAP add to this evidence base and I eagerly look forward to seeing the full results. The REMAP-CAP team are to be congratulated on completing this evaluation under difficult conditions.”
Prof Derek Hill, Professor of medical imaging science, UCL, and expert in medical devices, said:
“The arthritis drug tocilizumab attracted considerable interest early in the pandemic as a way of reducing severity of COVID symptoms. It was approved for treating patients in China during their first wave and also used in Italy in March. However results of clinical studies have been mixed and the benefit has been controversial.
“This most recent evidence for a benefit of tocilizumab comes from preliminary unpublished data and should treated with caution. However if the initial results stand up to full analysis and peer review then it could well be a valuable addition to the armoury of treatments that can help improve outcomes for COVID patients.”
https://www.imperial.ac.uk/news/209033/arthritis-drug-effective-treating-sickest-covid-19/
All our previous output on this subject can be seen at this weblink:
www.sciencemediacentre.org/tag/covid-19
Declared interests:
Prof Martin Landray: – Co-chief investigator of the RECOVERY trial of potential treatments for COVID-19 (funded by UKRI and NIHR; contributions to supply of study treatment from Abbvie, Roche, and Regeneron).
– Research funding to University of Oxford received from Novartis, Boehringer Ingelheim, and Merck Sharp & Dohme.-
– Infrastructure and core funding received from Health Data Research UK, NIHR Oxford Biomedical Research Centre, UK Biobank Ltd, MRC Population Health Research Unit, and British Heart Foundation Centre for Research Excellence.
– Employee of University of Oxford with salary supported by Li Ka Shing Foundation, Health Data Research UK, NIHR Oxford Biomedical Research Centre, Wellcome Trust, and National Health Service.
– I do not accept personal honoraria payments directly or indirectly from the pharmaceutical, biotechnology, or food industries although reimbursement to the University of Oxford for the costs of travel and accommodation to participate in scientific meetings may be accepted. I hold no shares in and receive no consultancy payments directly or indirectly from tobacco, pharmaceutical, biotechnology, or food companies. I comply with the Independence of Research Policy of the Nuffield Department of Population Health, Universityy of Oxford. For details see: https://www.ndph.ox.ac.uk/files/about/ndph-independence-of-research-policy-jun-20.pdf/@@download
Prof Athimalaipet Ramanan: “I am part of a group which has just completed an RCT of Tocilizumab in India (TOCIVIN study). I have also received speaker fees/Honoraria from Roche and participated/led trials of Tocilizumab in other conditions.”
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.”
Prof Peter Horby: “Chief Investigator of the RECOVERY trial. The RECOVERY trial is supported by a grant to the University of Oxford from UK Research and Innovation and NIHR (MC_PC_19056 ). Tocilizumab is being studied in RECOVERY. Tocilizumab was provided free of charge for this study by Roche. Lopinavir–ritonavir was provided free of charge for this study by Abbvie. REGN-COV2 was provided free of charge for this study by Regeneron.
Employee of University of Oxford with salary supported by Wellcome Trust and NIHR.
I do not accept any personal honoraria payments directly or indirectly from the pharmaceutical, biotechnology, or food industries.
I hold no shares in and receive no consultancy payments directly or indirectly from tobacco, pharmaceutical, biotechnology, or food companies.”
None others received