An initial crop of clinical trials testing an anti-inflammatory drug against COVID-19 do not look promising.
The best available evidence among these trials “doesn’t show that this drug is beneficial,” says Adarsh Bhimraj, an infectious diseases physician at the Cleveland Clinic, who was not involved in the research.
The drug, tocilizumab, is a treatment for the painful joint swelling that occurs in rheumatoid arthritis and is also used to manage a dangerous side effect of the cancer treatment CAR-T cell therapy (SN: 6/27/18). So clinical trials have been assessing whether tocilizumab might help COVID-19 patients by taming excessive inflammation as it does for these other two conditions.
The drug works by blocking the activity of a protein called interleukin 6, which contributes to the immune system’s inflammatory response. High levels of this protein, known as a cytokine, are a harbinger of severe disease in COVID-19 patients, studies have found.
Of the four clinical trials that have just reported peer-reviewed results on tocilizumab for COVID-19, only one meets the “gold standard” for evaluating a drug. Such randomized, double-blinded controlled trials randomly assign patients to receive a drug or a placebo, and don’t reveal to participants or doctors who is getting which.
In the trial with this design, tocilizumab did not reduce the risk of intubation or death as of four weeks compared with the placebo, researchers reported online in the New England Journal of Medicine on October 21. The study included 243 participants hospitalized with COVID-19 at seven Boston hospitals. Two-thirds received the drug, while the remainder received the placebo; participants also got other available drugs for COVID-19, such as remdesivir (SN: 5/13/20).
Two other trials randomly assigned which participants received tocilizumab but did not use a placebo, and it was clear whether patients were receiving the drug or not. This knowledge can bias the interpretation of some measures of how a patient is faring.
One of these two studies had mixed results. Tocilizumab may have reduced the likelihood of patients needing ventilation or dying as of two weeks compared with those who didn’t receive the drug. But there was no difference in mortality between the two groups at four weeks, researchers reported online October 20 in JAMA Internal Medicine. In the trial of 131 patients with COVID-19 pneumonia at nine hospitals in France, about half got tocilizumab along with regular care (such as antiviral drugs), while the remainder received just regular care.
The other study of 126 patients in 24 hospitals in Italy found that the drug didn’t appear to stop the disease from getting worse compared with standard care, researchers reported in JAMA Internal Medicine, also on October 20. About half the patients with COVID-19 pneumonia got the drug. The other half received standard care but could get tocilizumab if their condition worsened.
“The data from randomized controlled trials published to date do not support routine use of tocilizumab in patients hospitalized with COVID-19,” says Carolyn Calfee, a pulmonary and critical care specialist at the University of California, San Francisco School of Medicine, who was not involved in the trials.
There are some blanks still to be filled in, though. The trials didn’t evaluate patients with the most severe forms of COVID-19, namely those with acute respiratory distress syndrome on a ventilator, Calfee says. It’s also unclear whether categorizing patients by how much their interleukin 6 level is elevated might help identify patients who could benefit from the drug, she says.
The only study that found tocilizumab helpful had a weaker design. It was an observational study, so not randomized. The participants who received the drug had different characteristics from those who didn’t, which makes it difficult to determine whether the results are due to the drug or other factors. By 30 days, the risk of mortality was lower for hospitalized patients who took the drug in the first two days upon admission than for patients who didn’t, researchers report online October 20 in JAMA Internal Medicine.
Bhimraj says results from the remaining “gold standard” clinical trials still under way will be needed to better understand whether tocilizumab has a use in treating COVID-19. One trial offered preliminary results in a news release and reported that participants were less likely to need intubation or die with the drug (SN: 9/22/20).