Tocilizumab reduces systemic inflammation in comatose out-of-hospital cardiac arrest
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Tocilizumab, an interleukin-6 inhibitor, successfully reduced systemic inflammation and cardiac injury in resuscitated comatose patients with out-of-hospital cardiac arrest compared with placebo, according to results of the IMICA trial.
These findings were previously published in Trials.
“The IMICA trial was designed to improve post-resuscitation care by attempting to ameliorate the post-cardiac arrest syndrome,” Martin A. S. Meyer, MD, of the department of cardiology at Rigshospitalet and the Copenhagen University Hospital, Denmark, said during a presentation at the Resuscitation Science Symposium at the American Heart Association Scientific Sessions. “As part of the post-cardiac arrest syndrome, patients develop a high degree of systemic inflammation.”
For this randomized trial, researchers assigned 80 comatose adult patients with out-of-hospital cardiac arrest to receive a single infusion of the interleukin (IL)-6 receptor antibody tocilizumab (Actemra, Genentech) or placebo. The researchers hypothesized that tocilizumab may reduce systemic inflammation and risk for organ injury.
The primary endpoint was C-reactive protein level measured from hospital arrival through 72 hours.
“CRP was chosen as the primary endpoint as it is the downstream marker for many inflammatory processes, and its production is directly regulated by IL-6,” Meyer said during the presentation.
The secondary endpoints were markers of inflammation; MI, myocardial injury and dysfunction; and survival and neurological outcome after 6 months.
At 72 hours after hospital admission, CRP levels were approximately 96% lower among the tocilizumab group compared with the placebo group (95% CI, –97 to –94; P < .0001).
At 48 hours, levels of leucocytes were approximately 23% lower in the tocilizumab group (95% CI, –36 to –8; P = .004), but the association was not significant by 72 hours.
Levels of troponin (–36%; 95% CI, –54 to –11; P = .0082) and creatine (–38%; 95% CI, –53 to –19; P = .0006) were reduced at 12 hours in patients who received tocilizumab compared with those who received placebo.
At 48 hours, myocardial stress, measured as N-terminal pro-B-type natriuretic peptide levels, was also lower in the tocilizumab group (–65%; 95% CI, –80 to –41; P = .0002).
Neither survival (log-rank P = .9) or neurological outcomes (X2 P = .9) were significantly different at 180 days between the tocilizumab and placebo groups.
“These results led us to the promising conclusion that treatment with tocilizumab resulted in a significant reduction in systemic inflammation and cardiac injury in resuscitated, comatose out-of-hospital cardiac arrest patients,” Meyer said during the presentation.
Reference:
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Meyer MAS, et al. AOS.01; Late-Breaking Resuscitation Science. Presented at: American Heart Association Scientific Sessions; Nov. 13-17, 2020 (virtual meeting).
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