Tocilizumab associated with lower mortality among ventilated patients with COVID-19
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Mechanically ventilated patients with COVID-19 who received tocilizumab were 45% less likely to die, according to a single-center study published in Clinical Infectious Diseases.
“At this point in time, we would consider dexamethasone as the standard of care in mechanically ventilated patients but consider tocilizumab in nonresponders or when risks of steroid therapy for a particular patient outweigh the potential benefits,” Jason M. Pogue, PharmD, BCPS, BCIDP, clinical professor of infectious diseases at the University of Michigan College of Pharmacy, and Emily C. Somers, PhD, ScM, associate professor of internal medicine in the division of rheumatology at the University of Michigan Schools of Medicine and Public Health, told Healio.
Pogue, Somers and colleagues examined the safety and efficacy of IL-6 blockade with tocilizumab in 154 mechanically ventilated patients with COVID-19 admitted to Michigan Medicine. They gave 78 patients tocilizumab and placed 76 in a control group. They set survival probability after intubation as the study’s primary endpoint and performed a secondary analysis of superinfection rates.
Results showed that tocilizumab was associated with a 45% reduction in hazard of death (HR = 0.55; 95% CI, 0.33-0.9) and an increased proportion of patients with superinfections (54% vs. 26%; P < .001). Despite the increase in superinfections, the researchers found no difference in 28-day fatality rates among patients given tocilizumab with vs. without superinfection (22% vs. 15%; P = 0.42). They found that Staphylococcus aureus was responsible for half of bacterial pneumonia cases.
Pogue and Somers said they found the association between staphylococcal pneumonia in ventilated patients with COVID-19 “interesting,” and noted that patients given tocilizumab developed superinfections at twice the rates as the control group.
“While this increased risk of pneumonia was our primary potential concern with tocilizumab use, we were encouraged that the magnitude of survival benefit associated with tocilizumab held despite the infection risk, and that mortality was not higher in patients treated with tocilizumab who developed a superinfection compared to those who did not,” they said.
The researchers emphasized that one of the study’s major limitations was that treatment assignment was not randomized.
“Randomized controlled trials of tocilizumab, such as the RECOVERY trial, are ongoing, and we anxiously await their results,” Pogue and Somers said. “Our study focused on the most critically ill patients — those requiring mechanical ventilation — whereas trials may ultimately not have a high number of patients in this subset. Therefore, even when trial results become available, our data may be complementary.”
Perspective
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Gitanjali Pai, MD, AAHIVS
This study by Somers and colleagues is a promising observational report on the use of tocilizumab in mechanically ventilated patients with COVID-19. As our understanding of the disease pathophysiology increases, and especially during this unprecedented pandemic when we don’t have the luxury of time — it is important to explore treatment modalities other than just potential antivirals, and we have seen that reflected in recently published studies, eg, those examining steroids and IL-6 inhibitors. Early on in this pandemic, those patients who went on to require mechanical ventilation had a much higher mortality rate. It is heartening to note the 45% lower risk of mortality with the use of tocilizumab among mechanically ventilated patients with COVID-19. The higher risk of superinfections with this agent is not surprising in the setting of IL-6 inhibition by this agent. At a time when we are struggling with a lack of sufficient resources across the board, an increase in patients discharged home, and being able to be off the ventilator as demonstrated by the use of this agent does have implications as far as resource conservation, as outlined therein. Despite its limitations, the results of this study are encouraging as we look forward to further results from randomized control trials of IL-6 inhibitors. This is an all hands-on-deck moment, and we need to explore every potential tool in our armamentarium against COVID-19.
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