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A trial in Brazil published in the BMJ suggests adding the arthritis drug tocilizumab to standard care for patients in hospital with severe or critical COVID-19 is no better than standard care alone in improving clinical outcomes.
Prof Peter Horby, Professor of Emerging Infectious Diseases in the Nuffield Department of Medicine, University of Oxford, and Joint Chief Investigator for the RECOVERY trial, said:
“This study of tocilizumab in severely ill COVID patients is small and although the primary result is negative, the range of the result (the confidence limits) are compatible with either a significant harm or a significant benefit. There is a surprisingly low fatality, with only three percent of patients in the control group dying. Such a low rate is unusual in severely ill COVID patients and suggests that the death rate in the control group may be a chance finding which has affected the result. Much larger trials are needed to resolve the continuing uncertainty about the role of tocilizumab in the treatment of patients with COVID.”
Prof Martin Landray, Professor of Medicine and Epidemiology at the Nuffield Department of Population Health, University of Oxford, and Joint Chief Investigator for the RECOVERY trial, said:
“This paper reports a randomised trial of tocilizumab + usual care vs. usual care alone, conducted in Brazil in mid-2020. It is a small study including 129 patients. Like a number of small trials of tocilizumab published previously, it showed no clear difference in the number of patients progressing to mechanical ventilation or death. Within 28 days of randomisation, 14 patients in the tocilizumab group and 6 patients in the usual care group had died, a difference that is not statistically significant.
“It is important to consider the totality of the evidence: In total just over 2,000 patients with COVID-19 have been enrolled in published trials of tocilizumab, including REMAP-CAP. Taken together, these trials suggest that there may be a modest reduction in the risk of death of about one-sixth. But this is not statistically significant. It is also uncertain whether the presence or extent of any beneficial effect varies in different types of patient (for example those requiring invasive mechanical ventilation vs. those requiring oxygen alone).
“The RECOVERY trial has now randomised over 3,500 patients with COVID-19 tocilizumab vs. usual care alone, including large numbers of patients requiring artificial ventilators. Recruitment is ongoing and results are anticipated during the course of the next few weeks.”
Prof Anthony Gordon, Professor of Anaesthesia and Critical Care and NIHR Research Professor, Imperial College London, and UK Chief Investigator of the REMAP-CAP trial, said:
“The investigators of this study should be congratulated for undertaking and publishing results from a randomised controlled trial so that we can learn more about the use of tocilizumab in COVID-19. Unfortunately, this study has a number of limitations that prevent us from drawing definitive conclusions. The study was small and included patients with a wide range of illness severities.
“Although the investigators saw more deaths in the treated patients, it should be noted the “standard care” group only included two patients (3%) who died. Compared to all other studies of COVID-19 patients in hospital, this is a surprisingly low number. It raises the strong possibility that the results are susceptible to the play of chance, especially considering the low numbers in the overall trial, in a varied group of patients. As the investigators themselves conclude, their data doesn’t rule out the possibility of either benefit or harm from tocilizumab treatment.
“In summary, this study illustrates why it is important to conduct large randomised controlled trials and that evidence across all studies should be considered when making treatment decisions for different groups of patients. The international REMAP-CAP trial has recently reported benefit from tocilizumab treatment in critically ill patients with COVID.”
‘Effect of tocilizumab on clinical outcomes at 15 days in patients with severe or critical coronavirus disease 2019: randomized controlled trial’ by Viviane C Veiga et al. was published in the BMJ at 23:30 UK time on Wednesday 20 January 2021.
DOI: 10.1136/bmj.n84
Declared interests
Prof Peter Horby: “Co-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.”
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, University of Oxford. For details see: https://www.ndph.ox.ac.uk/files/about/ndph-independence-of-research-policy-jun-20.pdf/@@download.”
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.”