Infectious Disease

Canakinumab improves the chances of survival without ventilation in severe COVID-19. Not

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The researchers report that Novartis is being funded. Caricchio also reports on Janssen grants and personal fees from Janssen, GlaxoSmithKline, Bristol Myers Squibb, Eli Lilly & Co. and Siemens. Please refer to the study for all relevant financial information from the other authors.

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Canakinumab does not significantly increase the likelihood of survival without concomitant invasive mechanical ventilation compared to placebo in patients with severe COVID-19, according to data published in JAMA.

“IL-1 is an upstream proinflammatory cytokine that is involved in the pathogenesis of a variety of autoinflammatory diseases and induces the production of secondary inflammatory mediators, including IL-6.” Roberto Caricchio, MD, from the Lewis Katz School of Medicine at Temple University in Philadelphia, and colleagues wrote. “In-vitro experiments have shown that an infection with SARS-CoV-2 triggers the activation of the inflammasome and the maturation and release of IL-1.”

Canakinumab does not significantly increase the likelihood of survival without invasive mechanical ventilation compared to placebo in patients with severe COVID-19, according to data from Caricchio R, et al. JAMA. 2021; doi: 10.1001 / jama.2021.9508.

“Post-mortem examination of the lungs of patients who died of COVID-19 pneumonia revealed intense inflammation,” they added. “Immune profiling studies have shown that IL-1 is one of the inflammatory cytokines that define the ‘core signature of COVID-19’.”

To investigate the effectiveness of the IL-1 inhibitor canakinumab (Ilaris, Novartis) in patients admitted to hospital with severe COVID-19, Caricchio and colleagues conducted the CAN-COVID study. According to the researchers, this phase 3 randomized, double-blind, placebo-controlled study enrolled 454 participants with COVID-19 pneumonia from 39 hospitals in Europe and the United States.

Roberto Caricchio

The patients also showed hypoxia, which did not require invasive mechanical ventilation, and systemic hyperinflammation, which is defined by increased blood concentrations of C-reactive protein or ferritin. They were enrolled between April 30, 2020 and August 17, 2020 with the last primary endpoint assessment being on September 22, 2020.

Participants were randomized 1: 1 to receive either a single intravenous infusion of canakinumab at a dose of 450 mg for people weighing less than 60 kg, 600 mg for people weighing 60-80 kg, and 750 mg for people over 80 kg or placebo. The primary endpoint was survival without invasive mechanical ventilation from day 3 to day 29. Secondary endpoints included mortality related to COVID-19 and biomarker measurements for systemic hyperinflammation and safety.

According to the researchers, 88.8% of participants in the canakinumab group survived without requiring ventilation, compared with 85.7% of those who received a placebo, with a rate difference of 3.1% (95% CI, -3 , 1% to 9.3%) and a probability ratio of 1.39 (95% CI, 0.76-2.54). Meanwhile, 4.9% of participants in the canakinumab group experienced COVID-19-related mortality compared to 7.2% in the placebo group, with a rate difference of -2.3% (95% CI , -6.7% to 2.2%) and an odds ratio of 0.67 (95% CI, 0.3-1.5).

Serious adverse events were observed in 16% of those treated with canakinumab compared with 20.6% in the placebo group.

“In this multicenter, double-blind, placebo-controlled, randomized clinical trial conducted in 39 hospitals in Europe and the US, the IL-1 inhibitor canakinumab increased the likelihood of survival without [invasive mechanical ventilation] among patients hospitalized with severe COVID-19, ”wrote Caricchio and colleagues. “These results were also consistent for the secondary endpoint of COVID19-related mortality.”

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