corona virus-Covid19

COVID-19: Targeted Anti-Inflammatory Tocilizumab Reduced Mortality in Critically Ill Patients Interview with:

David E. Leaf, MD, MMSc, FASN Assistant Professor of Medicine, Harvard Medical School Director of Clinical and Translational Research in Acute Kidney Injury Division of Renal Medicine, Brigham and Women's Hospital

Dr. Leaf

David E. Leaf, MD, MMSc, FASN
Assistant Professor of Medicine, Harvard Medical School
Director of Clinical and Translational Research in Acute Kidney Injury
Division of Renal Medicine, Brigham and Women’s Hospital What is the background for this study?

Response: The data for this study were derived from a multicenter cohort study of over 4,000 critically ill patients with COVID-19 admitted to ICUs at 68 sites across the US, as part of the Study of the Treatment and Outcomes in Critically Ill Patients with COVID-19 (STOP-COVID). STOP-COVID was initiated by David E. Leaf, MD, MMSc and Shruti Gupta, MD, MPH, from the Division of Renal Medicine at Brigham and Women’s Hospital and Harvard Medical School. It was initiated in March, 2020 as an unfunded, grassroots network, and now includes over 400 collaborators from 68 sites across the US.

Using this data, we used a ‘target trial emulation’ approach to examine whether early administration of the monoclonal antibody, tocilizumab, reduces mortality in critically ill patients with COVID-19. Target trial emulation, a novel method of analyzing observational data, is the idea of simulating a randomized control trial to reduce bias. How does Tocilizumab differ from other therapeutics for COVID-19?

Response: Other anti-inflammatory drugs, namely dexamethasone (a steroid), have also been demonstrated to have beneficial effects in patients with COVID-19. However, unlike steroids, which dampen the immune system more broadly and can lead to secondary infection and other side effects, tocilizumab is a more targeted anti-inflammatory therapy. It acts on a specific pro-inflammatory cytokine pathway (IL-6). What are the main findings? 

Response: We found that patients who received tocilizumab in their first two days of ICU admission had a 30% relative reduction in the risk of death compared to patients who treatment did not include early use of tocilizumab. The beneficial effect of tocilizumab on survival was consistent across categories of age, sex, and illness severity, and was also observed in patients who either did or did not receive corticosteroids. Notably, we found that patients with a more rapid disease trajectory, defined as three days or fewer from symptom onset to ICU admission, appeared to benefit from tocilizumab to a greater extent than patients with a slower disease trajectory (the relative reduction in mortality with tocilizumab in this population was 60%). These subgroup findings, though, should be interpreted cautiously, and require confirmation by randomized clinical trials. What should readers take away from your report?

Response: Our findings suggest that tocilizumab is a promising therapy to reduce mortality in critically ill patients with COVID-19, particularly in those with a rapid disease trajectory (short duration from symptom onset to ICU admission). What recommendations do you have for future research as a result of this work?

Response: Ultimately, randomized clinical trials (RCTs) are needed to establish efficacy. The RCTs of tocilizumab that have been performed in COVID-19 to date have focused on patients with milder illness severity, and found mixed results. Our study, in contrast, exclusively examined critically ill patients. Future research should focus on this population.

We are grateful to our 400+ collaborators who dedicated countless hours to collect the data that made this study possible.


Gupta S, Wang W, Hayek SS, et al. Association Between Early Treatment With Tocilizumab and Mortality Among Critically Ill Patients With COVID-19. JAMA Intern Med. Published online October 20, 2020. doi:10.1001/jamainternmed.2020.6252 


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Last Updated on October 21, 2020 by Marie Benz MD FAAD