Ann Arbor, MI—A rheumatoid arthritis drug is showing promise in combating “cytokine storm” in patients critically ill with COVID-19.
The report in Clinical Infectious Diseases notes that Michigan Medicine patients who received a single dose of IV tocilizumab to calm their overreacting immune system were 45% less likely to die overall. In addition, according to University of Michigan researchers, they were more likely to be discharged or off a ventilator 1 month after treatment, compared with those who didn’t receive the drug.
Researchers emphasize that the reduced mortality risk was despite the fact that those patients were also twice as likely to develop an additional infection on top of the novel coronavirus.
Background information in the article notes that “severe COVID-19 can manifest in rapid decompensation and respiratory failure with elevated inflammatory markers, consistent with cytokine release syndrome for which IL-6 blockade is approved treatment.”
The study team looked at the effectiveness and safety of tocilizumab in a single-center cohort of patients with COVID-19 requiring mechanical ventilation. Defined as the primary endpoint was survival probability postintubation, while secondary analyses included an ordinal illness severity scale integrating superinfections.
Included in the study were 154 patients, with 78 receiving tocilizumab and 76 not getting the drug. Median follow-up was 47 days (range 28-67). Review of data showed that, when used, the drug usually was initiated within the 24-hour period surrounding intubation.
The two groups were similar, although tocilizumab-treated patients were younger (mean age 55 vs. 60 years), less likely to have chronic pulmonary disease (10% vs. 28%), and had lower D-dimer values at time of intubation (median 2.4 vs. 6.5 mg/dL).
In adjusted models, tocilizumab was found to be associated with a 45% reduction in hazard of death (hazard ratio 0.55; 95% CI 0.33, 0.90) and improved status on the ordinal outcome scale (odds ratio per 1-level increase: 0.58 [0.36, 0.94]).
“Though tocilizumab was associated with an increased proportion of patients with superinfections (54% vs. 26%; P <0.001), there was no difference in 28-day case fatality rate among tocilizumab-treated patients with versus without superinfection (22% vs. 15%; P = 0.42). Staphylococcus aureus accounted for ~50% of bacterial pneumonia,” the authors write.
Researchers conclude, “In this cohort of mechanically ventilated COVID-19 patients, tocilizumab was associated with lower mortality despite higher superinfection occurrence.”
“For a retrospective, single-center study, our data are robust. But 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,” explained senior author Jason Pogue, PharmD. “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.”
Dr. Pogue adds that a single dose of tocilizumab is roughly 100 times more expensive than a course of dexamethasone.
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The report in Clinical Infectious Diseases notes that Michigan Medicine patients who received a single dose of IV tocilizumab to calm their overreacting immune system were 45% less likely to die overall. In addition, according to University of Michigan researchers, they were more likely to be discharged or off a ventilator 1 month after treatment, compared with those who didn’t receive the drug.
Researchers emphasize that the reduced mortality risk was despite the fact that those patients were also twice as likely to develop an additional infection on top of the novel coronavirus.
Background information in the article notes that “severe COVID-19 can manifest in rapid decompensation and respiratory failure with elevated inflammatory markers, consistent with cytokine release syndrome for which IL-6 blockade is approved treatment.”
The study team looked at the effectiveness and safety of tocilizumab in a single-center cohort of patients with COVID-19 requiring mechanical ventilation. Defined as the primary endpoint was survival probability postintubation, while secondary analyses included an ordinal illness severity scale integrating superinfections.
Included in the study were 154 patients, with 78 receiving tocilizumab and 76 not getting the drug. Median follow-up was 47 days (range 28-67). Review of data showed that, when used, the drug usually was initiated within the 24-hour period surrounding intubation.
The two groups were similar, although tocilizumab-treated patients were younger (mean age 55 vs. 60 years), less likely to have chronic pulmonary disease (10% vs. 28%), and had lower D-dimer values at time of intubation (median 2.4 vs. 6.5 mg/dL).
In adjusted models, tocilizumab was found to be associated with a 45% reduction in hazard of death (hazard ratio 0.55; 95% CI 0.33, 0.90) and improved status on the ordinal outcome scale (odds ratio per 1-level increase: 0.58 [0.36, 0.94]).
“Though tocilizumab was associated with an increased proportion of patients with superinfections (54% vs. 26%; P <0.001), there was no difference in 28-day case fatality rate among tocilizumab-treated patients with versus without superinfection (22% vs. 15%; P = 0.42). Staphylococcus aureus accounted for ~50% of bacterial pneumonia,” the authors write.
Researchers conclude, “In this cohort of mechanically ventilated COVID-19 patients, tocilizumab was associated with lower mortality despite higher superinfection occurrence.”
“For a retrospective, single-center study, our data are robust. But 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,” explained senior author Jason Pogue, PharmD. “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.”
Dr. Pogue adds that a single dose of tocilizumab is roughly 100 times more expensive than a course of dexamethasone.
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