Treatment of critically ill COVID-19 patients with drugs commonly used for rheumatoid arthritis may significantly improve survival, a special study has found.
The findings, announced in January and now peer-reviewed and published in the New England Journal of Medicine, derived from the REMAP-CAP trial, which evaluates the effect of treatments on a combination of survival and the length of time patients need support in an intensive care unit (ICU).
Initial findings reported in November showed that tocilizumab, a drug used to treat arthritis, appeared to improve outcomes among very poor COVID-19 patients. But the effect on patient survival and time duration on organ support in ICU was not clear at that time.
The full, peer-reviewed analysis shows that tocilizumab and a second drug called sarilumab – the two types of immune modulators called IL-6 receptor antagonists – have a significant effect on patient survival, mortality reduction 8.5%.
In addition, the treatment improved rehabilitation so that patients could be discharged from the intensive care unit (ICU) about a week earlier.
“We are very pleased that our full results have now been published following a peer review. This confirms the strength of our conclusions, that tocilizumab and sarilumab can reduce deaths by almost a quarter, in the sickest patients with COVID, ”said Dr Anthony Gordon, Chair in Anesthesia and Critical Care at Imperial College London and Consultant in Intensive Care Medicine at Imperial College Healthcare NHS Trust.
“We also saw that it helped speed up recovery, so that patients were discharged from the ICU a week earlier and left hospital two weeks earlier. It’s good news to know We have found that several thousand patients have benefited from the use of these drugs within the NHS, and other studies have now confirmed our results so that even more patients will benefit.
“We are very grateful to all the NHS staff who helped bring the case to fruition and to all the patients and their families who agreed to take part in this trial. Together we are all helping to deal with this terrible disease. “
Tocilizumab and sarilumab are immunosuppressive drugs used to treat rheumatoid arthritis. They were two of several immune modification therapies included in the REMAP-CAP trial. At the end of last year, positive early decisions about tocilizumab were released before the full data were collected. With the full analysis now available, researchers are confident that the findings will continue to provide clinical benefit to the sickest patients with COVID-19.
Overall results
At the time of the full study 353 patients were assigned to tocilizumab, 48 to sarilumab and 402 to control. Most patients were treated with corticosteroids and were receiving respiratory support.
The test data gave an odd ratio of 1.64 for a better outcome with tocilizumab, and 1.76 for sarilumab, compared to no immune modification, with a high level of statistical confirmation (> 99.5% probability that both treatments are better than immune change).
Hospital mortality was 27.3% among patients receiving IL-6 receptor agonists (28.0% for tocilizumab, 22.2% for sarilumab) compared with 35.8% for control group. This means that for every 12 patients treated, one life would be saved.
Dr Gordon said: “Previous trials using IL-6 receptor agonists have not shown a clear benefit of either disease progression or survival in COVID-19 patients, but these studies did provide included less severe patients who began treatment at different stages of the disease course.
“Perhaps an important difference in our study was that patients with severe disease were registered within 24 hours of starting organ support. This clarifies a possible early window. for treatment where the sickest patients get the most out of immune modeling treatment. “
Study co-author Christopher Seymour, MD, associate professor of critical care and emergency medicine at the University of Pittsburgh School of Medicine (UPMC), said: “As soon as the results of an immune modulator hit our statistical vigor, these drugs became immediate introduction by UPMC and North American REMAP-CAP partners as our standard treatment for critically ill COVID-19 patients.
“In addition, the overall design of REMAP-CAP allows us to test multiple interventions simultaneously and over time. Thus, while implementing new evidence-based care practices , we will continue to test other promising treatments in patients with moderate to severe COVID- 19. “
The REMAP-CAP study is led by Imperial College London and the National Intensive Care Research and Research Center (ICNARC) in the UK and Utrecht University Medical Center in Europe. He began researching treatments for COVID-19 in March 2020, enrolling in hospital patients with moderate or severe infection (requiring ICU care) COVID-19.
The study design randomized patients to many combinations of treatments, allowing researchers to evaluate different treatments for COVID-19, including antiviral, drugs that alter the response immune, and medications that alter or support other critical aspects of the body ‘s response to the virus.
To date, more than 5,500 patients in 15 countries have been enrolled at more than 290 hospitals worldwide and randomized to multiple treatment combinations. The effects of interventions are evaluated separately for moderate and severely ill patients.
Recent findings on tocilizumab and sarilumab complement REMAP-CAP findings from earlier this year, which found that hydrocortisone steroid treatment improved recovery among critically ill COVID-19 patients .
This study is one of several COVID-19 studies that have received emergency public health research status by the Department of Health and Social Care. In February 2021 75% of study participants were employed in the UK through the NIHR Clinical Research Network (CRN).
The study is supported in the UK by the National Institute for Health Research (NIHR) and Imperial College London & ICNARC are partners in the EU-funded PREPARE consortium.
* This is an updated press release, based on results from January 2021 * https: /
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NOTES TO EDITORS
‘Interleukin-6 Receptor Antagonists in Covid-19 Abusive Patients’ by REMAP-CAP Analysts published in the New England Journal of Medicine.
* Reduction in mortality measured using combined hospital mortality for both IL-6 receptor antagonist (27.3% (108/395) versus control (35.8% (142/397)). Mortality was hospitals 28.0% (98/350) for tocilizumab, 22.2% (10/45) for sarilumab.Eleven patients remain to be followed.
** Effect of Hydrocortisone on organ mortality and support in patients with severe COVID-19, JAMA, 2020 – https: /
In REMAP-CAP
REMAP-CAP (The Random-Based Adaptive Multifactorial Platform for Community Acquired Pneumonia) is an ongoing variable clinical trial involving more than 3000 COVID-19 patients at more than 290 clinical sites all over the world.
REMAP-CAP continues to evaluate several other research questions, including therapeutic anticoagulation, antiplatelet drugs, apremilast, eritoran, anakinra, vitamin C, simvastatin, convalescent plasma, macrolides, and antibiotics.
For more information, see the ICNARC REMAP-CAP website https: /
About Imperial College London
Imperial College London is one of the leading universities in the world. The College’s 20,000 students and 8,000 staff are working to solve the biggest challenges in science, medicine, engineering and industry.
Imperial is the fifth most international university in the world, according to Times Higher Education, with academic links to more than 150 countries. Reuters has named the College as the most innovative university in the UK because of its unique entrepreneurial culture and connection to industry.
Imperial staff, students and alumni are working around the clock to counter COVID-19. Imperial has nearly two thousand key employees, and is at the forefront of coronavirus epidemiology, virology, vaccine development and diagnosis. More than a thousand Imperial staff and students volunteer to support the NHS. http: // www.
In NIHR
The National Institute for Health Research (NIHR) is the nation’s largest funder of health and care research. The NIHR:
- Funding, supporting and delivering high quality research that benefits the NHS, public health and social care
- Engaging and involving patients, carers and the public to improve the accessibility, quality and impact of research
- Attracting, training and supporting the best researchers to address complex future health and care challenges
- Invest in world-class infrastructure and a skilled delivery team to turn findings into better treatments and services
- Partners with other public funders, charities and business to get the most out of patient research and the economy
The NIHR was established in 2006 to improve the health and well-being of the country through research, and is funded by the Department of Health and Social Care. In addition to its national role, the NIHR supports applied health screening for the direct and basic benefit of people in low- and middle-income countries, drawing on UK support from the UK government.