This drug reduces excessive inflammatory responses from patients receiving immunotherapy. Researchers initially used the drug called tocilizumab monoclonal antibody against tocilizumab to treat patients with the most severe symptoms especially those experiencing a risk immune response called cytokine storms-which seems to improve survival especially among patients who require mechanical ventilation. Encouraged by these results clinicians began using this drug to patients with mild illness aimed at helping them avoid mechanical ventilation.
Clinical researchers reported their findings in June 15th in Chest magazine.
Price says that over inflammation caused by T cell immunotherapy in some cancer patients resembles cytokine storms in COVID-19. In patients with the most severe illness, this condition causes respiratory failure and death.
The researchers speculate that topirazumab can inhibit CRS, reduce life-threatening inflammation and prevent patients from needing mechanical ventilation.
“We chose this drug for biological reasons,” Price said. “A series of small clinical reports in other countries suggest that topirazumab may be able to treat severe inflammation in patients with COVID-19. Our expertise in the use of the drug at Yale and the growing use of biological agents in immune disorders, coupled with the availability of the drug, guided our decision.”
This study is by far the largest clinical series of COVID-19 patients treated with topirazumab. The study examined the first batch of 239 COVID-19 patients hospitalized by YNHH, of whom 153 were treated with topirazumab.
The team found that COVID-19 CRS patients who received topirazumab had a lower overall mortality than those reported by other hospitals, especially those with CRS who needed mechanical ventilation, which is usually a poor prognostic indicator. The 14-day survival rate of patients treated with topirazumab was 87%, and most of them met the COVID-19 criteria for critical hospitalization. The 48 patients who received topirazumab who needed mechanical ventilation used a ventilator for an average of five and a half days, and their 14-day survival rate was 75%.
“normally, at least half of patients who need mechanical ventilation die, but only 25 percent of patients who use tosizumab die,” said Maricar Malinis, Ph.D., an associate professor of medicine and one of the senior authors of the study.
In all studies, the mortality rate of COVID-19 patients who needed ventilator was between 40 and 90 per cent.
To determine which COVID-19 patients will receive medication, the Yale team designed an algorithm to identify patients who appear to have CRS based on the amount of oxygen required and indicators of inflammation.
“This strategy is very different-we usually treat infectious diseases, not the consequences,” said Dr. Jeff Topal, an associate professor of medicine and infectious disease expert who oversees hospital drug prescriptions.
The use of algorithms “democratizes treatment by focusing on clinical manifestations rather than patients,” said Dr. Frederick L. Altice, a professor of medicine and public health. So, unlike other places, the mortality rate of people of color is lower than that of whites. ”
Because the team observed that topirazumab was safe and showed promising results in the most severe COVID-19 patients, they began to use it in patients with mild conditions but signs of excessive inflammation. The aim is to reduce the possibility of mechanical ventilation.
“once a patient needs mechanical ventilation, his performance is poor,” said Charles Dela Cruz, an associate professor of internal medicine (lung and intensive care) who specializes in respiratory infections. “in the absence of clinical trials, the worst consequences of using safe drugs to prevent COVID-19 are reasonable.”
Despite the surge in COVID-19 patients during the study period (March and April), the number of patients requiring mechanical ventilation is not expected to increase at the same time. The use of topirazumab seems to prevent COVID-19 patients from developing mechanical ventilation, which never exceeds 18% of the hospital’s capacity.
Other Yale studies and prospective clinical trials are expected to further confirm the effect of topirazumab on the prognosis of patients.