Effect of Canakinumab on Survival Outcomes Without Invasive Mechanical Ventilation in Patients Hospitalized With Severe COVID-19

Senior woman wearing mask infected by coronavirus on hospital bed receiving medicine by drip. Close-up fingers of the senior patient ´s hand while she is sleeping. Horizontal photo
In a phase 3 randomized trial, researchers assessed the effects of canakinumab treatment on survival outcomes in patients hospitalized with severe COVID-19 who did not require invasive mechanical ventilation.

Among patients hospitalized with severe COVID-19, treatment with canakinumab did not significantly increase the likelihood of survival without the need for invasive mechanical ventilation (IMV) after 29 days, according to study results published in JAMA.

In this phase 3, double-blind, placebo-controlled randomized trial (ClinicalTrials.gov identifier: NCT04362813) conducted between April and August 2020 at 39 hospitals in Europe and the United States, researchers evaluated the efficacy of canakinumab in patients hospitalized with severe COVID-19.  A total of 454 patients were randomly assigned in a 1:1 fashion to receive either a single weight-adjusted dose of canakinumab (n=227) or placebo (n=227). All patients received standard care treatment for COVID-19. Per study protocol, the use of immunomodulatory therapies targeting interleukin-1 (IL-1), IL-6, or tumor necrosis factor were not allowed.

The primary outcome was survival without IMV between day 3 and day 29, with COVID-19-related mortality as the secondary outcome.

At baseline, demographics and disease characteristics were similar between the canakinumab and placebo groups. The median age was 59 years, and one-third third of patients were 65 years of age and older. Approximately 50% of the patients were obese, and 70% were receiving low-flow oxygen via mask or nasal prongs. On or after day 1, dexamethasone was given to 14.5% and 22.5% of patients in the canakinumab and placebo groups, respectively; and, convalescent plasma was administered in 6.6% and 13.2% of patients in the canakinumab and placebo groups, respectively.

Of the 454 patients enrolled in the study, 6 patients were lost to follow-up, resulting in 225 patients in the canakinumab group and 223 in the placebo group. By day 29, the percentage of patients who survived without IMV was similar between the 2 groups: 88.8% vs 85.7% (odds ratio [OR], 1.39; 95% CI, 0.76-2.54; P =.29). COVID-related mortality occurred in 4.9% of patients in the canakinumab group vs 7.2% in the placebo group (OR, 0.67; 95% CI, 0.30-1.50).

Severe adverse events occurred in 16% of patients in the canakinumab group vs 20.6% in the placebo group.

The study was limited by the evolving standard of care and outcomes in the early period of the COVID-19 pandemic. In addition, there was an imbalance in the use of prohibited therapies, such as tocilizumab and anakinra, after the study therapy was initiated.

Disclosure: This study was sponsored by Novartis Pharma AG, Basel, Switzerland. All authors received funding from Novartis during the conduct of the study. Please see the original reference for a full list of authors’ disclosures.


Caricchio R, Abbate A, Gordeev I, et al; CAN-COVID Investigators. Effect of canakinumab vs placebo on survival without invasive mechanical ventilation in patients hospitalized with severe COVID-19: a randomized clinical trial. JAMA. 2021;326(3):230-239. doi:10.1001/jama.2021.9508