Critically-ill coronavirus patients could leave intensive care up to 10 days earlier if given one of two arthritis drugs, research suggests.
In November, scientists from Imperial College London reported how intravenously administering the rheumatoid arthritis medication tocilizumab improved intensive care patient outcomes by 87%, defined as how dependent the individual was on organ support and surviving hospital admission.
It was then unclear whether tocilizumab boosted overall survival or reduced the time a patient required organ support.
The latest findings have revealed giving tocilizumab or fellow rheumatoid arthritis drug sarilumab – typically on top of standard of care steroids – enabled a patient to leave intensive care between seven and 10 days earlier, compared to those who just received standard care.
These drugs were also linked to an 8.5% reduced risk of death, which the scientists called “a big change in survival”.
They are said to be in discussion with the UK department of health, with tocilizumab and sarilumab expected to be recommended for use in the near future.
The preliminary results are yet to be published in a peer-reviewed journal, but appear on the pre-print website medRxiv.
“This is a significant finding which could have immediate implications for the sickest patients with COVID-19 [the disease caused by the coronavirus],” said study author Professor Anthony Gordon.
“We found that among critically ill adult patients, those receiving breathing support in intensive care, treatment with these drugs can improve their chances of survival and recovery.
“At a time when hospitalisations and deaths from COVID-19 are soaring in the UK, it’s crucial we continue to identify effective treatments which can help to turn the tide against this disease.”
On 7 January, more than 52,000 new people tested positive for the coronavirus in the UK, a 33.8% increase on the past week.
Hospitalisations and deaths were also up 37% and 28.9%, respectively.
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At the time of the analysis, 353 patients had been given tocilizumab, 48 were on sarilumab and the remaining 402 acted as controls on standard of care.
Overall, around 80% of the patients were given steroids, according to co-author Dr Lennie Derde.
The NHS began administering the steroid dexamethasone after a study in June suggested the low-cost drug cut the risk of death among patients on ventilation by a third.
Steroids are “generally anti-inflammatory”, whereas tocilizumab and sarilumab specifically block the immune-fighting – but also inflammatory – protein interleukin-6.
These so-called “IL-6 receptor antagonists” are therefore more “specific” treatments, according to Professor Gordon.
Research has shown the sickest coronavirus patients have a substantial amount of inflammation in their lungs, which may come about if the immune system goes into overdrive after encountering the infection.
The “vast majority” of the study’s participants received a single infusion of tocilizumab or sarilumab, however, a second dose of tocilizumab may have been administered if deemed necessary by doctors.
Results reveal 27% of the patients on tocilizumab or sarilumab survived, compared to 35.8% in the control group.
To put that into context, Professor Gordon said: “You treat 12 patients and you will save one life.”
“Steroids are recommended for patients who need oxygen,” he added.
“If the patients become sicker and need more breathing support, you add in this medication [tocilizumab or sarilumab] and get added benefit.”
Past coronavirus studies into tocilizumab have thrown up mixed results, with none showing the drug improved death rates up to 30 deaths after its administration.
“Previous trials using IL-6 receptor antagonists have showed no clear benefit on either disease progression or survival in COVID-19 patients, but those studies included less severely-ill patients and started treatment at different stages in the disease course,” said Professor Gordon.
“A crucial difference may be that in our study, critically-ill patients were enrolled within 24 hours of starting organ support.
“This highlights a potential early window for treatment where the sickest patients may gain the most benefit from immune modulation treatment.”
Tocilizumab was used in China – where the coronavirus emerged – in January, as well as in Italy – Europe’s former outbreak epicentre – in March.
The scientists are in conversation with the department of health about recommending these drugs for critically-ill coronavirus patients.
“My understanding is they will become available so we can immediately start treating patients with these drugs,” said Professor Gordon.
One of the key advantages of dexamethasone is its low cost, at around £5 ($6.78) per dose, typically given over 10 days.
While tocilizumab and sarilumab are more expensive at between £750 ($1,017) and £1,000 ($1,355) per infusion, Professor Gordon pointed out a day in intensive care can cost close to £2,000 ($2,711).
The ongoing study continues to look for different potential therapies, with more than 3,900 moderately or severely-ill patients across 15 countries having been enrolled to date.
In 2020, the scientists found the steroid hydrocortisone improved recovery among critically-ill coronavirus patients.
Speaking of the latest results, Professor Peter Horby from the University of Oxford said: “It is great to see a positive result at a time that we really need good news and more tools to fight COVID.”
Professor Martin Landray – also from University of Oxford – agreed the findings are “good news”, but added “there are, of course, still unanswered questions”.
“For example, exactly how well does tocilizumab work in different types of patients?,” he said.
“And if given earlier, might it reduce the need for patients to require mechanical ventilation in the first place?”
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