Canakinumab Trial in Patients Hospitalized With Severe COVID-19
- 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.
Is canakinumab, an anti–interleukin (IL)-1β antibody, effective for the treatment of severe coronavirus disease 2019 (COVID-19) pneumonia in hospitalized patients?
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.
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%)
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.
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.
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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