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A review of studies in the use of tocilizumab in treating Covid-19

Irish Society for Rheumatology Spring Meeting, Virtual, 13 May 2021

Consultant Paediatric Rheumatologist at the Bristol Royal Hospital for Children and Royal National Hospital for Rheumatic Diseases, Prof A V Ramanan, is currently leading clinical trials of tocilizumab, a biologic usually associated with the treatment of rheumatoid arthritis, for the treatment of Covid-19. Prof Ramanan spent 20 years working on haemophagocytic syndrome (HPS), a rare immune disease, which is seen mostly in children, but increasingly in adults. Primary manifestations of the condition appear in children, while the secondary haemophagocytic syndrome occurs as a cytokine storm in adults.

Prof A V Ramanan

During his presentation at the ISR Spring Meeting, Prof Ramanan highlighted that there is a clear case for IL-6 playing a key role in the pathophysiology of Covid-19. He proceeded to review a number of important papers published on the connection between tocilizumab and Covid-19. The first paper to pique his interest was published in
October 2020 and titled ‘Association between early treatment with tocilizumab and mortality among critically-ill patients with Covid-19’. In this study, almost 4,000 critically-ill patients with laboratory confirmed Covid-19 were studied. Of this number, 433 received tocilizumab within two days of being admitted to ICU.

Primary manifestations of the condition appear in children, while the secondary haemophagocytic syndrome occurs as a cytokine storm in adults

This study showed that those who were treated with tocilizumab had a much higher survival rate than those who did not receive it. Another study, carried out in France, titled ‘Effect of tocilizumab vs usual care in adults hospitalised with Covid-19 and moderate or severe pneumonia’ involved 130 patients, 63 of whom were administered tocilizumab. In this group, by day 14 there was less need for invasive mechanical ventilation or non-invasive ventilation and fewer members of the tocilizumab group died compared to the control group. Prof Ramanan noted that this was “a significant result, even though it was a small sample size”, as the first controlled trial data in relation to tocilizumab in Covid-19.

Other studies were less positive. For example, a study of 243 patients from Boston, published in the New England Journal of Medicine, reported no significant effect on disease progression, reduction in the need for ventilation or death. Yet another, in 452 patients with severe Covid-19 pneumonia, revealed mixed results. The primary endpoint was not achieved and they did not find a difference in mortality. However, there was an improvement in the discharge time and a lower risk of clinical failure. Furthermore, this study found that there were no new risks introduced through the use of tocilizumab.

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