Two drugs used to treat rheumatoid arthritis could help to save the lives of intensive care patients with severe Covid, researchers have found.
Early results from the international trial previously suggested tocilizumab might improve outcomes for those with life-threatening coronavirus infections. However, other trials reported mixed results.
Now further results from a larger group of patients not only confirm the drug brings benefits but reveal that another arthritis drug, sarilumab, appears to do the same, not only saving lives but cutting the length of time patients spent in intensive care.
Prof Anthony Gordon, of Imperial College London, the UK’s chief investigator on the trial behind the findings, said he expected the drugs to be used in patients in the UK imminently.
“My understanding is they will become available so that we can immediately start treating patients in the intensive care units with these drugs so that they can start having immediate effects,” he said.
Both tocilizumab and sarilumab are what are known as IL-6 receptor antagonists, which dampen down the effect of proteins that can cause an overreaction of the immune system. Severe Covid has previously been linked to dangerous levels of inflammation in the body.
The new results, which have not yet undergone peer review, come from a clinical trial known as Remap-Cap (the randomized embedded multifactorial adaptive platform for community acquired pneumonia) that involves more than 3,900 Covid patients in 15 countries around the world.
The latest study reveals how researchers randomised adult Covid patients to receiving standard care, or an intravenous infusion of tocilizumab or sarilumab, within 24 hours of being put on organ support in intensive care. Fewer patients were given sarilumab since the drug became available for use later than tocilizumab.
The researchers then monitored the patients’ progress for at least 21 days.
The results from 792 patients across six countries reveal that tocilizumab and sarilumab reduced the risk of death.
While hospital mortality stood at 35.8% (142/397) for patients given standard care, it was 28.0% (98/350) for tocilizumab and 22.2% (10/45) for sarilumab. Combining the results for the two drugs gave a hospital mortality of 27.3% (108/395) – an 8.5 percentage point drop in absolute risk – or a 24% relative reduction – in the risk of death compared with the group who had standard care.
“Treat 12 patients and you save one life,” said Gordon. “[That’s] a big effect.”
The team also found those given tocilizumab or sarilumab recovered more quickly, leaving intensive care about seven to 10 days earlier than those who had standard care.
Dr Lennie Derde, intensive care consultant and European coordinating investigator of the Remap-Cap trial, said the international nature of the trial was important, given the worldwide impact of the pandemic.
“The results are applicable not just in the UK but across the globe,” she said.
Peter Horby, professor of emerging infectious diseases and global health at Oxford University, who leads the Recovery trial to test drugs for treating Covid patients but was not involved in Ramap-Cap, said the results were good news, noting that until now only the steroids dexamethasone and hydrocortisone have been found to save lives among Covid patients on ventilators. Such drugs also act to suppress inflammation and the immune system.
With about 80% of the patients in the Remap-Cap trial also given dexamethasone or another steroid, Horby said it appears that tocilizumab and sarilumab provide an addition benefit.
“We saw an absolute reduction in the risk of death in mechanically ventilated patients of about 12% with dexamethasone [in the Recovery trial], and here you are seeing an absolute reduction of about 8% – that would seem to be on top of the [effect of] dexamethasone,” said Horby.
But Horby stressed the findings only applied to critically ill patients, while tocilizumab and sarilumab are far more expensive than dexamethasone: tocilizumab and sarilumab cost about £750 to £1,000 per patient, compared with about £5 for dexamethasone.
However, Gordon said the therapies were still cost-effective given the lives they would save and the impact on time spent in intensive care.
“A day in the intensive care unit can cost close to £2,000 a day,” he said.
The deputy chief medical officer, Prof Jonathan Van-Tam, said: “This is a significant step forward for increasing survival of patients in intensive care with Covid-19. The data shows that tocilizumab, and likely sarilumab, speed up and improve the odds of recovery in intensive care, which is crucial for helping to relieve pressure on intensive care and hospitals and saving lives.”
