Combining steroids with arthritis drug almost halves deaths among critically-ill coronavirus patients, study suggests

Combining steroids with an arthritis drug almost halves a critically-ill coronavirus patient's death risk, research suggests.

In November 2020, 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.

Two months later, the same scientists revealed giving tocilizumab or fellow rheumatoid arthritis drug sarilumab – typically on top of steroids – could enable a patient to leave intensive care up to 10 days earlier.

A University of Oxford study now suggests combining tocilizumab with a steroid cuts the risk of death by around a third in patients who require oxygen and have a significant amount of inflammation.

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Among those on mechnical invasive ventilation, the two-drug regimen could nearly halve patient fatalities, the results show.

The preliminary Oxford results are yet to be published in a peer-reviewed journal, but appear on the pre-print website medRxiv.

Enthusiasm for tocilizumab was initially tempered after studies failed to demonstrate whether it reduced a coronavirus patient's death risk.

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"Previous trials of tocilizumab had shown mixed results and it was unclear which patients might benefit from the treatment," said Professor Peter Horby, joint chief investigator of the University of Oxford study.

"We now know the benefits of tocilizumab extend to all COVID [the disease caused by the coronavirus] patients with low oxygen levels and significant inflammation.

"The double impact of dexamethasone [a steroid] plus tocilizumab is impressive and very welcome."

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The ongoing Oxford trial, called RECOVERY, has been testing potential coronavirus treatments since March 2020. More than 35,000 patients across 177 NHS hospitals have been enrolled to date.

Tocilizumab was added to the trial that April for patients who required oxygen and had worringly high markers of inflammation in their blood.

More than 2,000 patients were randomly allocated to receive intravenous tocilizumab, with their outcomes being compared against a similar number of indiviuduals who had "usual care" alone.

Overall, more than four in five (82%) of the study's participants were given a steroid, like the low-cost dexamethasone.

RECOVERY results released in June 2020 revealed dexamethasone cut the risk of death among patients on mechanical ventilators by a third, prompting the NHS to administer it as the standard of care.

Mechanical ventilation occurs when a tube is inserted into the airways to deliver oxygen to the lungs, while removing carbon dioxide. Non-invasive ventilation involves an oxygen-emitting mask being fitted over the nose and mouth, but no tube.

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Steroids are anti-inflammatory in a fairly general way, whereas tocilizumab specifically blocks the infection-fighting – but also inflammatory – protein interleukin-6. It is therefore considered a more targeted treatment.

Research has shown the sickest coronavirus patients have a substantial amount of inflammation in their lungs, which may come about if their immune system goes into overdrive after encountering the infection.

One of the key advantages of dexamethasone is its low cost, at around £5 ($6.91) per dose, typically given over 10 days.

Professor Andrew Gordon, who was involved in the Imperial research, previously said tocilizumab costs between £750 ($1,036) and £1,000 ($1,381) per infusion. A patient usually requires one hour-long infusion, according to Professor Martin Landray, joint chief investigator of the Oxford study.

A day in intensive care can cost close to £2,000 ($2,763), added Professor Gordon.

The latest RECOVERY results reveal 29% of the patients in the tocilizumab group died within 28 days of the drug being administered, compared with 33% of those just receiving the usual care.

"This means for every 25 patients treated with tocilizumab, one additional life would be saved," wrote the scientists.

Tocilizumab also increases a patient's chance of being discharged alive within 28 days by 23%, the results suggest.

These benefits were observed among all the patients, including those requiring oxygen via a face mask and the individuals on mechanical ventilators in intensive care.

Among those who were not on mechanical ventilation when enrolled onto the trial, tocilizumab reduced the odds of them progressing onto the machine or dying by 15%, the results suggest.

There is no evidence, however, tocilizumab helps patients on ventilators successfully come off the machine, which essentially breathes for them while they fight off the coronavirus.

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When combining the results with previous steroid-coronavirus studies, the Oxford scientists extrapolated the duo-treatment could cut the risk of death by a third among patients on oxygen and close to half for those on ventilators.

"The results from the RECOVERY trial clearly show the benefits of tocilizumab and dexamethasone in tackling the worst consequences of COVID-19; improving survival, shortening hospital stay and reducing the need for mechanical ventilators," said Professor Landray.

"Used in combination, the impact is substantial.

"This is good news for patients and good news for the health services that care for them in the UK and around the world."

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One who understands the benefits of tocilizumab all too well is Wendy Coleman, 62.

Coleman was given the drug as part of the RECOVERY trial when she was admitted to Chesterfield Royal Hospital with severe coronavirus complications in 2020.

"I was struggling to breathe quite badly and on the verge of being placed in an intensive care unit when I was asked if I wanted to take part in the RECOVERY trial," she said.

"After I was given tocilizumab, my condition stabilised and I didn't get any worse.

"Up until then it was quite scary as I didn't know if I was going to make it or not.

"You never think about clinical trials until you are in need of these treatments and then you realise what happens behind the scenes to find out if they work."

Tocilizumab was used in China – where the coronavirus emerged – in January 2020, as well as in Italy – Europe's former outbreak epicentre – that March.

Speaking of the results, Professor Fiona Watt from the Medical Research Council – which funded the research along with the National Institute for Health Research – said: "It's incredibly encouraging doctors now have an additional COVID-19 treatment that can save lives and reduce the length of hospital stays.

"Importantly, the benefits from tocilizumab are in addition to those provided by dexamethasone; patients receiving both drugs do even better than patients on dexamethasone alone.

"This world-leading study shows the power of well-designed clinical trials to discover which drugs can help patients."