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Interleukin-6 antagonists improve outcomes in hospitalised COVID-19 patients

Findings from a study published today [6 July] in the Journal of the American Medical Association (JAMA) have prompted new World Health Organization (WHO) recommendations to use interleukin-6 antagonists in patients with severe or critical COVID-19 along with corticosteroids.

A new analysis of 27 randomised trials involving nearly 11,000 patients found that treating hospitalised COVID-19 patients with drugs that block the effects of interleukin-6 (the interleukin-6 antagonists tocilizumab and sarilumab) reduces the risk of death and the need for mechanical ventilation.

The study, which was coordinated by WHO in partnership with King’s College London, University of Bristol, University College London and Guy’s and St Thomas’ NHS Foundation Trust, found that interleukin-6 antagonists were most effective when administered with corticosteroids. In hospitalised patients, administering one of these drugs in addition to corticosteroids reduces the risk of death by 17%, compared to the use of corticosteroids alone. In patients not on mechanical ventilation, the risk of mechanical ventilation or death is reduced by 21%, compared to the use of corticosteroids alone.

In severely ill COVID-19 patients, the immune system overreacts, generating cytokines such as interleukin-6. Clinical trials have been testing whether drugs that inhibit the effects of interleukin-6, such as tocilizumab and sarilumab, benefit hospitalised patients with COVID-19. These trials have variously reported benefit, no effect and harm.

This prompted researchers from WHO’s Rapid Evidence Appraisal for COVID-19 Therapies [REACT] Working Group, to examine the clinical benefit of treating hospitalised COVID-19 patients with interleukin-6 antagonists, compared with either a placebo or usual care. They combined data from 27 randomised trials that were conducted in 28 countries.

This analysis included information on 10,930 patients, of whom 6,449 were randomly assigned to receive interleukin-6 antagonists and 4,481 to receive usual care or placebo.

Results showed that the risk of dying within 28 days is lower in patients receiving interleukin-6 antagonists. In this group, the risk of death is 22% compared with an assumed risk of 25% in those receiving only usual care.

Importantly, improvements in outcomes were greater in patients who also received corticosteroids. In these patients, the risk of dying within 28 days is 21% in patients receiving interleukin-6 antagonists compared with an assumed 25% in patients receiving usual care. This means that for every 100 such patients, four more will survive.

The study also looked at the effect of these drugs on whether patients progressed to mechanical ventilation or death. Among patients also treated with corticosteroids, the risk was found to be 26% for those receiving interleukin-6 antagonists compared with an assumed 33% in those receiving usual care. This means that for every 100 such patients, 7 more will survive and avoid mechanical ventilation.

Commenting on the results of the analysis Dr Janet Diaz, Lead for Clinical management, WHO Health Emergencies, said: “Bringing together the results of trials conducted around the world is one of the best ways to find treatments that will help more people survive COVID-19. We have updated our clinical care treatment guidance to reflect this latest development. While science has delivered, we must now turn our attention to access. Given the extent of global vaccine inequity, people in the lowest income countries will be the ones most at risk of severe and critical COVID-19. Those are the people these drugs need to reach.”

Prof Manu Shankar-Hari, Critical Care Consultant at Guy’s and St Thomas’ Hospital NHS Foundation Trust, Professor of Critical Care Medicine at King’s College London and a NIHR Clinician Scientist, said: “COVID-19 is a serious illness. Our research shows that interleukin-6 antagonists reduce deaths from COVID-19, i.e. save lives, and prevent progression to severe illness necessitating breathing support with a ventilator. Further, interleukin-6 antagonists appear even more effective when used alongside corticosteroids. Our research findings reflect the incredible research effort from scientists worldwide since the start of the pandemic. On a personal note, I am grateful to the patients and their families for their willingness to participate in research during these challenging times.”

Jonathan Sterne, Professor of Medical Statistics and Epidemiology, University of Bristol, Deputy Director of the National Institute for Health Research Bristol Biomedical Research Centre (NIHR Bristol BRC) and Director of Health Data Research UK South West, said: “Clinical trials assessing the efficacy of monoclonal antibodies that block interleukin-6 in hospitalised patients with COVID-19 have variously reported benefit, no effect and harm. By rapidly combining 95 per cent of the worldwide data from these trials, we have shown that these drugs work consistently in reducing death and severe COVID-19 disease across countries and health care settings, and that they work better among patients who are also receiving corticosteroids.”

Claire Vale, Principal Research Fellow at the MRC Clinical Trials Unit at UCL (University College London), said: “These results, which will lead to better outcomes for patients hospitalized with COVID-19, reflect a huge global effort.  Bringing together this information in such a short space of time has only been possible thanks to the overwhelming commitment of all the doctors and teams who ran the trials, and of course, the patients who took part in them.”

Paper

‘Association between administration of interleukin-6 antagonists and mortality among hospitalized patients with COVID-19: a meta-analysis’ by Shankar-Hari M, Vale C, J Sterne et al in JAMA.

Notes to editors:

Link to WHO guidance (new guidance will be available at 20 H CEST on 6 July 2021): https://apps.who.int/iris/bitstream/handle/10665/342368/WHO-2019-nCoV-therapeutics-2021.2-eng.pdf)

Media contacts

The World Health Organization

For further information or to arrange an interview with Dr Janet Diaz, please contact mediainquiries@who.int

Guy’s and St Thomas’ NHS foundation Trust and King’s College London

For further information or to arrange an interview with Professor Manu Shankar-Hari, please contact Ania Rainbird, Head of R&D Communications at Guy’s and St Thomas’ NHS Foundation Trust, email: ania.rainbird@gstt.nhs.uk, mobile: +44 (0) 7789552399 or Rebecca Lewis, Senior News and Campaigns Manager, King’s College London, email:  rebecca.s.lewis@kcl.ac.uk, mobile 07961046728

University of Bristol / NIHR Bristol Biomedical Research Centre

For further information or to arrange an interview with Professor Jonathan Sterne, please contact Victoria Tagg [Monday /Tuesday] email victoria.tagg@bristol.ac.uk, tel: + 44 (0)117 4284576, Caroline Clancy [Wed to Fri], email caroline.clancy@bristol.ac.uk, mobile: +44 (0)7776 170238.

UCL

For further information or to arrange an interview with Claire Vale, please contact the UCL Media Relations team – Mark Greaves, m.greaves@ucl.ac.uk +44 (0) 7990 675 947 and Rowan Walker, rowan.walker@ucl.ac.uk, +44 (0) 7986 463767

About the World Health Organisation

The World Health Organization provides global leadership in public health within the United Nations system. Founded in 1948, WHO works with 194 Member States across six regions, to promote health, keep the world safe and serve the vulnerable. Our goal for 2019-2023 is to ensure that a billion more people have universal health coverage, to protect a billion more people from health emergencies, and provide a further billion people with better health and well-being.

For updates on COVID-19 and public health advice to protect yourself from coronavirus, visit www.who.int and follow WHO on Twitter, Facebook, Instagram, LinkedIn, TikTok, Pinterest, Snapchat, YouTube, Twitch

About Guy’s and St Thomas’ NHS Foundation Trust

Guy’s and St Thomas’ provides 2.6 million patient contacts in acute and specialist hospital services and community services every year. As one of the biggest NHS trusts in the UK, with an annual turnover of almost £1.6 billion, we employ around 22,000 staff. www.guysandstthomas.nhs.uk

About King’s College London

King’s College London is one of the top 35 UK universities in the world and one of the top 10 in Europe (QS World University Rankings, 2020/21) and among the oldest in England. King’s has more than 31,000 students (including more than 12,800 postgraduates) from some 150 countries worldwide, and some 8,500 staff.

King’s has an outstanding reputation for world-class teaching and cutting-edge research. In the 2014 Research Excellence Framework (REF), eighty-four per cent of research at King’s was deemed ‘world-leading’ or ‘internationally excellent’ (3* and 4*).

Since our foundation, King’s students and staff have dedicated themselves in the service of society. King’s will continue to focus on world-leading education, research and service, and will have an increasingly proactive role to play in a more interconnected, complex world. Visit our website to find out more about Vision 2029, King’s strategic vision to take the university to the 200th anniversary of its founding.

About NIHR Bristol BRC
NIHR Bristol Biomedical Research Centre’s (NIHR Bristol BRC) innovative biomedical research takes science from the laboratory bench or computer and develops it into new drugs, treatments or health advice. Its world-leading scientists work on many aspects of health, from the role played by individual genes and proteins to analysing large collections of data on hundreds of thousands of people. Bristol BRC is unique among the NIHR’s 20 BRCs across England, thanks to its expertise in ground-breaking population health research.

About the University of Bristol

The University is ranked within the top 10 universities in the UK and top 60 in the world (QS World University Rankings 2021); it is also ranked among the top five institutions in the UK for its research, according to analysis of the Research Excellence Framework (REF) 2014; and is the 7th most targeted university by top UK employers.

The University was founded in 1876 and was granted its Royal Charter in 1909.  It was the first university in England to admit women on the same basis as men.

The University is a major force in the economic, social and cultural life of Bristol and the region, but is also a significant player on the world stage. It has over 20,000 undergraduates and over 7,000 postgraduate students from more than 100 countries, and its research links span the globe.

UCL – University College London

UCL is a diverse community with the freedom to challenge and think differently.

Our community of more than 41,500 students from 150 countries and over 12,500 staff pursues academic excellence, breaks boundaries and makes a positive impact on real world problems.

We are consistently ranked among the top 10 universities in the world and are one of only a handful of institutions rated as having the strongest academic reputation and the broadest research impact.

We have a progressive and integrated approach to our teaching and research – championing innovation, creativity and cross-disciplinary working. We teach our students how to think, not what to think, and see them as partners, collaborators and contributors.

For almost 200 years, we are proud to have opened higher education to students from a wide range of backgrounds and to change the way we create and share knowledge.

We were the first in England to welcome women to university education and that courageous attitude and disruptive spirit is still alive today. We are UCL.

www.ucl.ac.uk| Follow @uclnews on Twitter | Watch our YouTube channel | Listen to UCL podcasts on SoundCloud | Find out what’s on at UCL Minds | #MadeAtUCL

Find out how UCL is helping lead the global fight against COVID-19 www.ucl.ac.uk/covid-19-research

About the National Institute for Health Research

The mission of the National Institute for Health Research (NIHR) is to improve the health and wealth of the nation through research. We do this by:

  • Funding high quality, timely research that benefits the NHS, public health and social care;
  • Investing in world-class expertise, facilities and a skilled delivery workforce to translate discoveries into improved treatments and services;
  • Partnering with patients, service users, carers and communities, improving the relevance, quality and impact of our research;
  • Attracting, training and supporting the best researchers to tackle complex health and social care challenges;
  • Collaborating with other public funders, charities and industry to help shape a cohesive and globally competitive research system;
  • Funding applied global health research and training to meet the needs of the poorest people in low and middle income countries.

NIHR is funded by the Department of Health and Social Care. Its work in low and middle income countries is principally funded through UK Aid from the UK government.

About Mahender Bansal

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