Earlier Intervention Pivotal in Seeing Better COVID-19 Outcomes

Roche recently reported tocilizumab for treatment of hospitalized adult patients with severe coronavirus 2019 (COVID-19) associated pneumonia did not meet the study’s endpoint.

However, in another study, the application of this Interleukin-6 inhibitor (IL6ri) was more efficacious in the treatment of COVID-19 with earlier interventions.

Specifically, 2 Boston physicians have done a statistical analysis and reported a reduction in intubation and mortality rates in COVID-19 patients when administering inhibitors, sarilumab or tocilizumab, earlier in the disease course.

Manish Sagar, MD, and Pranay Sinha, MD are infectious diseases physicians and researchers at Boston Medical Center, and have been working together in studying these inhibitors on patients admitted to their hospital. Sagar is also an associate professor of medicine and microbiology at Boston University School of Medicine.

Boston Medical Center serves as a safety net hospital and cares for a disadvantaged socioeconomic patient population with a large minority community. Their hospital was hit particularly hard during the onset of the COVID-19 pandemic, seeing approximately 2000 patients with the majority of them being seen between March and May.

Without the benefit of randomized, controlled studies at the very beginning of the pandemic, clinicians such as Sagar and Sinha were challenged to find therapies as they became inundated with severe cases of COVID-19. This led them to administering off-label medications to patients.

Their work in this area was recently published in a paper in the International Journal of Infectious Diseases.

Many months later, Sagar says there is still much to learn about the virus including the variations in the mortality rates in different populations, but there is a theoretical framework for how COVID-19 acts in some patients who can progress to more severe disease after suffering a cytokine storm.

“The first part of the disease is really driven by [the] virus and the second part is driven by an exuberant immune response,” Sagar said.

Sagar says the inhibitors were used to alter the immune response. “You are not stopping the virus, but you are stopping the exuberant immune response.”

The physicians made it clear this was not a randomized, controlled, trial, but for the patients they treated and received the inhibitors at an earlier intervention, they saw a better outcome in terms of mortality, according to Sinha. “The timing really, really mattered.”

The Boston Medical Center’s patients were broken into two groups: stage IIB and stage III based on their fraction of inspired oxygen (FiO2). Patients requiring up to 45 percent FiO2 were considered to be stage IIB and those more severe who were requiring greater than 45 percent FiO2 were considered to be stage III.

Once an appropriate patient was identified, they were given IL6ri (sarilumab or tocilizumab) based on iteratively reviewed guidelines.

The discharge rate was higher for the stage IIB group compared to the stage III group, showing the impact that earlier administration can have throughout the progression of COVID-19. The average length of stay in the hospital was 12.9 days, but patients treated in stage IIB had a shorter average length of stay (11.3 days) than those in stage III (15 days). A total of 68 patients (26.7 percent) required mechanical ventilation, and of these patients, 44 were intubated 24 hours later, after receiving IL6ri.

In the first segment of their Contagion® interview, Sagar and Sinha discuss what they experienced in their hospital and their insights on administering the inhibitors.