An initial harvest of clinical trials testing an anti-inflammatory against COVID-19 does not look promising.
The best evidence available among these trials "does not prove that this drug is beneficial," says Adarsh Bhimraj, an infectious disease doctor at the Cleveland Clinic who did not participate in the research.
The drug, tocilizumab, is a treatment for painful inflammation of the joints that occurs in rheumatoid arthritis and is also used to manage a dangerous side effect of CAR-T cell therapy for cancer treatment (SN: 27/06/18 ). Thus, clinical trials evaluated whether tocilizumab could help patients with COVID-19 to tame excessive inflammation as it does in these other two conditions.
The drug works by blocking the activity of a protein called interleukin 6, which contributes to the inflammatory response of the immune system. Studies have found that high levels of this protein, known as cytokine, are the harbinger of a serious disease in patients with COVID-19.
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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. These randomized, double-blind, controlled trials randomly assign patients to receive a drug or placebo and do not reveal to participants or physicians who is getting which.
In the trial with this design, tocilizumab did not reduce the risk of intubation or death to four weeks compared to placebo, online researchers reported in the New England Journal of Medicine on Oct. 21. The study included 243 participants hospitalized with COVID-19 in seven Boston hospitals. Two-thirds received the drug, while the rest received placebo; participants also received other medications available for COVID-19, such as remdesivir (SN: 13/05/20).
Two other trials randomly assigned participants who received tocilizumab but did not use placebo and it became unclear whether patients were receiving the drug or not. This knowledge may skew the interpretation of some measures of how a patient is doing.
One of these two studies had mixed results. Tocilizumab may have reduced the likelihood that patients will need ventilation or die after two weeks compared to those who have not received the drug. But there was no difference in mortality between the two groups at four weeks, the researchers reported online on Oct. 20 at JAMA Internal Medicine. In the trial of 131 patients with COVID-19 pneumonia in nine hospitals in France, approximately half received tocilizumab along with regular care (such as antivirals), while the rest received only regular care.
The other study of 126 patients in 24 hospitals in Italy found that the drug did not stop getting worse from the disease compared to standard care, as reported by researchers at JAMA Internal Medicine, also on October 20th. About half of patients with COVID-19 pneumonia got the drug. The other half received standard care, but could have tocilizumab if their condition worsened.
“Randomized controlled trial data published to date do not support routine use of tocilizumab in hospitalized patients with COVID-19,” says Carolyn Calfee, a pulmonary care specialist and critic at the University of California, San Francisco School of Medicine. does not participate in trials.
There are still some blanks to fill. The trials did not evaluate patients with the most severe forms of COVID-19, namely those with acute respiratory distress syndrome in a ventilator, Calfee says. From her, it is also unclear whether classifying patients by the high level of interleukin 6 can help identify patients who might benefit from the drug.
The only study that found tocilizumab useful was a weaker design. It was an observational study, so not randomized. Participants who received the drug had different characteristics from those who did not, making it difficult to determine whether the results were due to the drug or other factors. At 30 days, the risk of mortality was lower for hospitalized patients who took the drug in the first two days after admission than for patients who did not, according to online researchers Oct. 20 at JAMA Internal Medicine.
Bhimraj says the results of the remaining ongoing "gold standard" clinical trials will be needed to better understand whether tocilizumab is useful in the treatment of COVID-19. One trial offered preliminary results in a press release and reported that participants were less likely to need intubation or die with the drug (SN: 22/09/20).