Could IL-6 Inhibition Benefit Patients With Severe COVID-19?

Researchers behind a new observational study say they have found a "signal" of benefit for interleukin-6 (IL-6) inhibitors such as tocilizumab in reducing in-hospital mortality in COVID-19 patients.

Dr. Pranay Sinha of Boston University School of Medicine and colleagues analyzed data for 516 adults admitted to four safety-net hospital systems with COVID-19 and high rates of medical comorbidities; 104 patients (20.1%) received an IL-6 inhibitor as part of their treatment.

After adjusting for confounders, there was a 37% reduction in the odds of in-hospital mortality in those who received IL-6 inhibitor therapy compared with those who did not, although this was not statistically significant (odds ratio, 0.63; 95% confidence interval, 0.29 to 1.38), the researchers report in the Journal of Infectious Diseases.

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They note that the effect size observed in their cohort is similar to that demonstrated in another recent study from the U.S. It is also in line with the 40% and 45% risk reduction associated with IL-6-inhibitor therapy on combined endpoints of death and/or mechanical ventilation reported in two other studies.

Other studies, however, have not found significant benefits of IL-6 inhibition in severe COVID-19.

"The data do seem mixed at present although the consensus appears to be moving away from the effectiveness of IL-6 inhibitors. We think that these trials need to be analyzed with nuance," Dr. Sinha told Reuters Health by email.

"I think our findings bring in some fresh perspectives into the literature," he added.

"Firstly, since the patients studied in this group were at safety-net hospitals across the U.S., we were able to describe the effect of IL-6 inhibitors in a population that is underrepresented in the existing literature. Further, our population was quite diverse, which is crucial since there may be race-based difference in effectiveness of IL-6 inhibitors," Dr. Sinha said.

Researchers has also found hints that the timing of IL-6 inhibitors in COVID-19 may be related to the effectiveness of these drugs, with earlier administration associated with improved outcomes, Dr. Sinha said.

"We are awaiting data from many trials on IL-6 inhibitors," he said.

For now, the latest guidelines from the Infectious Diseases Society of America (IDSA) do not recommend routine use of tocilizumab in hospitalized patients with COVID-19. This is a conditional recommendation with low certainty of evidence.

At present, "I think most medical centers have shifted their treatment protocols to use dexamethasone instead of IL-6 inhibitors to quell the cytokine storms associated with COVID-19. I think dexamethasone is likely to remain first-line, but IL-6 inhibitors may still be helpful in a sub-population of patients. Analysis of patients who received IL-6 inhibitors in the RECOVERY trial will be illuminating, I believe," Dr. Sinha told Reuters Health.

The study had no commercial funding and the authors have declared no conflicts of interest.

—Megan Brooks

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