Arthritis Drug Calms COVID-19 Cytokine Storm, Reduces Mortality by 45%

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In a new observational, controlled study, the immunosuppressive drug tocilizumab showed a 45% reduction in mortality for COVID-19 patients on ventilators. While originally developed to treat rheumatoid arthritis, tocilizumab has been previously used to calm cytokine storm in patients receiving cancer immunotherapy treatment. The study, published in Clinical Infectious Diseases, suggests the drug has the same calming effect on the cytokine storm caused by the immune system's overreaction to SARS-CoV-2.

The study presented itself through random opportunity. From early March to late April, 154 critically ill patients requiring mechanical ventilation were treated at Michigan Medicine, University of Michigan's academic medical center. Since this was the early days of the pandemic and not much was known at the time, the Michigan Medicine Antimicrobial Stewardship Program stepped in to suggest possible treatment regimens. The physicians identified tocilizumab as a potential therapy for the most severely ill COVID-19 patients; but, it was merely a recommendation, leading half the doctors to use it while the other half did not. This inadvertently set the stage for an observational, controlled study.

Of the 154 COVID-19 patients on a ventilator, 78 received tocilizumab, and 76 did not. Most of the 78 patients received it within 24 hours of their intubation. Patients in the two groups were clinically similar, except for a slightly higher average age in the non-tocilizumab group, and lower rates of chronic obstructive pulmonary disease and chronic kidney disease among the tocilizumab patients.

According to the study results, 28 days after patients were intubated, 18% of those who received tocilizumab had died while 36% had not. Using a common regression model to adjust for other health characteristics, the researchers say this represents a 45% reduction in mortality. Additionally, of those still in the hospital at the end of the study period, 82% of the tocilizumab patients had come off the ventilator, compared with 53% of those who didn't receive the drug.

When the research team decided to look back at the data and see if any trends emerged, lead author Emily Somers, an epidemiologist who has studied both rheumatologic and immunologic diseases, admitted she was uncertain of what they would fine. One thing she did know—her team was in a unique position to answer a critically important question regarding COVID-10 treatments.

“One role of epidemiology is to rigorously evaluate real-world data on treatment effects, especially when evidence from clinical trials is not available,” Somers said. “We kept trying to prove ourselves wrong as signals of benefit emerged in the data, both because of the immediate implications of these data, and in part because of concern about the supply of the medication for other patients. But the difference in mortality despite the increase in secondary infection is quite pronounced, even after accounting for many other factors.”

The secondary infection Somers refers to occurred in 80% of patients—54% who took tocilizumab and 26% who did not. While these types of infections, mostly ventilator-associated pneumonia, usually reduce the change of survival for COVID-19 patients, the study did not reflect that and still revealed a positive effect of treatment with tocilizumab.

The authors acknowledge some study limitations and say more research is required, especially a randomized controlled drug trial that can confirm perceived benefits and better quantify risks. Additionally, after the conclusion of this study, a randomized controlled trial of 6,425 patients in the UK found that the steroid dexamethasone reduced deaths by 1/3 in ventilated patients and 1/5 in patients receiving oxygen only. A single dose of tocilizumab is roughly 100 times more expensive than a course of dexamethasone.

“At this time, due to the lack of randomized controlled trial data and the much higher cost, we recommend reserving tocilizumab for the treatment of select patients who decompensate while on or after receiving dexamethasone or in patients where the risks of adverse events from steroid therapy outweigh the potential benefits" says senior author Jason Pogue, Pharm.D., a member of the Antimicrobial Stewardship Program. “Further studies of tocilizumab, which is more targeted than dexamethasone in addressing the hyperinflammatory process, could include combining these agents or comparing them head-to-head.”

Pogue also notes that the drug sarilumab, which aims to treat cytokine storm by targeting the interleukin-6 (IL-6) receptor, appears to have failed to improve outcomes in a clinical trial in COVID-19 patients, including those on ventilators.