October 20, 2020

expert reaction to three studies of Tocilizumab to treat COVID patients

Three studies, published in JAMA Internal Medicine, looked at the drug Tocilizumab to treat COVID-19 patients.

Prof Martin Landray, Professor of Medicine & Epidemiology, Nuffield Department of Population Health, University of Oxford, said:

“Tocilizumab is an established treatment for rheumatoid arthritis and the so-called cytokine storm that occurs with some forms of cancer treatment. It blocks a specific part of the immune system, interleukin-6, and consequently reduces inflammation. 

“There is a reasonable hypothesis that dampening down the inflammatory overdrive that accompanies more severe forms of COVID might improve clinical outcomes for patients, particularly those who are already showing signs of lung damage with low blood oxygen levels. 

“The three papers reported here do little to resolve this question.  The largest is an observational study which compared 433 patients who had been given Tocilizumab by their doctors with those who had not. However, the doctors chose to give this treatment to patients who tended to be younger and whose lung damage was less severe – the types of patient you would expect to do better anyway. The statistical analyses attempt to deal with this mismatch but, as the authors point out, it is impossible to know whether the apparent benefit that is seen is due to a true benefit of the Tocilizumab treatment or is because there are persistent background differences between those who did and those who did not get given the treatment. The authors rightly conclude, ‘further research from randomized controlled trials is needed.’

“The other two papers do describe the results of randomised controlled trials. But here we have a different issue – the trials are too small to give robust answers, with each including fewer than 150 patients. 

“The headline results of previous randomised trials have been reported by Roche, the manufacturer of Tocilizumab. Those trials included around 400 patients each but gave mixed results. 

“Thus Tocilizumab remains a promising but unproven treatment. It may work, it may not, and it may only work in some types of patients. What is needed is evidence from randomised trials that are sufficiently large to provide doctors the information they need to treat future patients. 

“The RECOVERY trial will provide this information. To date, over 1200 hospitalised patients with severe COVID have been included, with half of those randomised to receive Tocilizumab and the half randomised to receive usual NHS care alone. Results are anticipated by the end of the year. Until that time, Tocilizumab remains promising but unproven.”

‘Effect of Tocilizumab vs Usual Care in Adults Hospitalized With COVID-19 and Moderate or Severe Pneumonia’ by Olivier Hermine et al.; ‘Effect of Tocilizumab vs Standard Care on Clinical Worsening in Patients Hospitalized With COVID-19 Pneumonia’ by Carlo Salvarani  et al; and ‘Association Between Early Treatment With Tocilizumab and Mortality Among Critically Ill Patients With COVID-19’ by Shruti Gupta et al were all published in JAMA Internal Medicine at 6pm UK TIME on Tuesday 20 October 2020.

Respectively:

JAMA Intern Med. doi:10.1001/jamainternmed.2020.6820

JAMA Intern Med. doi:10.1001/jamainternmed.2020.6615

JAMA Intern Med. doi:10.1001/jamainternmed.2020.6252

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, University of Oxford.  For details see: https://www.ndph.ox.ac.uk/files/about/ndph-independence-of-research-policy-jun-20.pdf/@@download.”