Arthritis drugs save lives of hospitalised Covid-19 patients

In the study, published in the Journal of the American Medical Association, researchers analysed 27 randomised trials involving nearly 11,000 patients. They found that treating hospitalised Covid-19 patients with drugs tocilizumab and sarilumab (the interleukin-6 antagonists) was most effective when administered with corticosteroids.

The WHO now recommends the use of these drugs along with corticosteroids in patients with severe or critical Covid-19.

One of the study’s lead authors, Dr Claire Vale (MRC Clinical Trials Unit at UCL), said: “These results, which will lead to better outcomes for patients hospitalised 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.

”I hope these findings ensure that Covid-19 patients worldwide will benefit from these drugs.”

The study, which was coordinated by WHO, found that in hospitalised patients, administering either tocilizumab or sarilumab in addition to corticosteroids reduced 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 was 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 only corticosteroids. 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 only corticosteroids. This means that for every 100 such patients, seven 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.”

Professor Manu Shankar-Hari (King’s College London), Critical Care Consultant at Guy’s and St Thomas’ Hospital NHS Foundation Trust, 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.”

Professor Jonathan Sterne, of the University of Bristol, 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.”

Links

• Full paper in JAMA
• New WHO Covid-19 treatment recommendations
• Blog post: Interlukin-6 antagonists improve outcomes in hospitalised COVID-19 patients
• Dr Claire Vale’s academic profile
• MRC Clinical Trials Unit at UCL
• Population Health Sciences

Image

Milad hospital in Iran during the Covid-19 pandemic. Credit: Mehr News Agency. CC-BY-4.0. Source: Wikimedia Commons.

Media contact

Mark Greaves

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E: m.greaves [at] ucl.ac.uk