Drugs typically used to treat rheumatoid arthritis can help critically ill Covid-19 patients in intensive care units, one new study finds.
But experts warn that more research is needed before doctors start using the drugs more widely, because another new study found that one of those drugs did not help patients hospitalized with Covid-19 pneumonia get significantly better.
The two studies were published in the New England Journal of Medicine on Thursday.
The drugs reduce inflammation and doctors hope they can help patients recover from the overwhelming immune response that Covid-19 sometimes triggers.
‘Patients recovered more quickly’
The study showing improvement among patients included data on more than 800 critically ill adults hospitalized with Covid-19 in intensive care units between March 9 and November 19 across six countries.
The patients were randomly assigned to receive infusions of either two rheumatoid arthritis drugs, tocilizumab or sarilumab, or receive the standard of care at the time, which included corticosteroids for most patients.
The international team of researchers found that patients who received either rheumatoid arthritis drug experienced significantly more days when they did not require organ support compared with those who received standard care.
The data showed that patients given tocilizumab had a median of 10 days when they did not need organ support and those given sarilumab had a median of 11 days. Patients who did not get either drugs had zero days free of organ support.
The researchers also found that 27% of patients who received either arthritis drug died in the hospital compared with 36% of those who received standard care.
“That’s a big change in survival,” Anthony Gordon, a senior investigator in the trial and a professor at Imperial College London in the United Kingdom, said previously about the research during a briefing in January.
“We also saw the patients recovered more quickly,” he said. “They were getting better and able to be discharged from the ICU quicker – and that was on average and every patient is slightly different.”
Some serious adverse events were reported during the study. Nine were among those given tocilizumab, including a bacterial infection, five bleeding events, two cardiac events and one person had deteriorating vision. Eleven adverse events were among those given standard care, including four bleeding events and seven cases of blood clotting. No serious adverse events were reported among those given sarilumab.
Even though the new study suggests that treatment with tocilizumab and sarilumab can improve outcomes for critically Covid-19 patients, the researchers noted that some separate studies previously found no benefit with tocilizumab.
“Many previously reported trials included less severely ill patients and excluded patients already receiving respiratory support,” the researchers wrote in the study. “In those trials, no clear evidence suggested that tocilizumab was effective at preventing disease progression, and no benefit with respect to survival was seen.”
‘How to best use them remains unclear’
The other study published in the New England Journal of Medicine on Thursday found that tocilizumab did not help hospitalized patients with Covid-19 pneumonia get “significantly better” or lower their chances of dying.
Among 452 patients who were randomly assigned to receive either a single intravenous infusion of tocilizumab or a placebo, the death rate at 28 days later was 19.7% in the tocilizumab group and 19.4% in the placebo group, according to the study’s abstract.
“In this trial involving hospitalized patients with severe Covid-19 pneumonia, we found no significant difference in clinical status between the tocilizumab group and the placebo group at day 28. No mortality benefit was associated with the use of tocilizumab, although the trial was not powered for this outcome,” wrote the researchers, from Baylor College of Medicine in Houston and several other institutions around the world.
Tocilizumab was well tolerated, the researchers say and their data suggest patients possibly benefited from the drug by seeing shorter stays in the hospital or intensive care units, though more research is needed to know for sure.
“The trial suggests that you are less likely to have a future need of a ventilator if you are admitted to the hospital for treatment,” Dr. Ivan Rosas, chief of pulmonary, critical care and sleep medicine in the department of medicine at Baylor College of Medicine and the lead author of the study, said in a news release on Thursday. “Although we did not find a significant improvement in clinical status, the study’s primary endpoint, reducing the number of hospital days is important for patients and for our healthcare system.”
An editorial that published alongside the two new studies on Thursday noted that various factors could explain why one trial showed improvement with tocilizumab, which belongs to a class of drugs called interleukin-6 inhibitors, while another study did not show improvement.
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Differences among the studies include patients’ severity of illness, the time at which treatment was given and the other types of treatment patients might have received, such as corticosteroids, Dr. Eric Rubin, editor-in-chief of the New England Journal of Medicine, and his co-authors Dr. Dan Longo and Dr. Lindsey Baden, wrote in the editorial.
“These points raise thorny issues,” the authors of the editorial write. “For now, we are left with evidence of benefit from interleukin-6 inhibitors, at least under some circumstances, but how to best use them remains unclear.”