Canakinumab Trial in Patients Hospitalized With Severe COVID-19

Quick Takes

  • Canakinumab did not improve survival without invasive mechanical ventilation in severe COVID-19 compared to placebo.
  • The study was limited by evolving standard of care and outcomes in the early period of the COVID-19 pandemic.

Study Questions:

Is canakinumab, an anti–interleukin (IL)-1β antibody, effective for the treatment of severe coronavirus disease 2019 (COVID-19) pneumonia in hospitalized patients?

Methods:

CAN-COVID was a multicenter, randomized, double-blind, placebo-controlled trial that enrolled patients hospitalized with COVID-19 pneumonia with evidence of hypoxemia not initially requiring invasive mechanical ventilation (IMV), and laboratory evidence of hyperinflammation (elevated C-reactive protein or ferritin levels). Patient were randomly assigned to receive a single intravenous dose of canakinumab or placebo in addition to local standard of care. Use of immunomodulatory therapies targeted against IL-1, IL-6, or tumor necrosis factor were not allowed. The primary outcome was survival without IMV. Secondary outcomes included COVID-19–related mortality, ratio of hyperinflammation biomarkers compared to baseline, and safety.

Results:

There were 454 patients enrolled and randomized into the study. The study reports the interim analysis of the patients who completed follow-up at 29 days.

The primary outcome for patients who survived without IMV was 88.8% (198 of 223) for the canakinumab group versus 85.7% (191 of 223) for placebo (odds ratio [OR], 1.39; 95% confidence interval [CI], 0.76-2.54; p = 0.29).

Key secondary outcomes for canakinumab versus placebo:

  • COVID-19–related mortality: 11 of 223 patients (4.9%) versus 16 of 222 (7.2%); odds ratio, 0.67 (95% CI, 0.30-1.50)
  • Serious adverse events: 36 of 225 (16%) versus 46 of 223 (20.6%)

Conclusions:

In patients hospitalized with COVID-19 pneumonia with evidence of hypoxemia not initially requiring IMV and hyperinflammation, canakinumab did not significantly improve survival without IMV compared to placebo at 29 days.

Perspective:

Given the high morbidity and mortality associated with severe COVID-19, especially among patients requiring IMV, there is a continued need to identify therapies to limit disease progression. Targeting systemic inflammation associated with COVID-19 has been a promising strategy. Therapies like dexamethasone and tocilizumab have previously been shown to improve outcomes. IL-1, which canakinumab targets, has been identified as possibly playing a key role in the inflammatory response in COVID-19. However, canakinumab did not achieve its primary endpoint in this study and does not have a clear role in the treatment of COVID-19, at least not in the setting of background standard of care, which includes established anti-inflammation therapies (i.e., dexamethasone). Limitations of the study include the evolving standard of care and outcomes during the study duration and use of prohibited therapies.

Clinical Topics: Dyslipidemia, Prevention, Lipid Metabolism

Keywords: Biological Markers, Coronavirus, COVID-19, C-Reactive Protein, Critical Illness, Disease Progression, Ferritins, Hypoxia, Brain, Immunomodulation, Inflammation, Interleukin-1 Receptor Accessory Protein, Pneumonia, Primary Prevention, Respiration, Artificial, Standard of Care, Ventilation


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