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Original Investigation
July 20, 2021

Effect of Canakinumab vs Placebo on Survival Without Invasive Mechanical Ventilation in Patients Hospitalized With Severe COVID-19: A Randomized Clinical Trial

Author Affiliations
  • 1Division of Rheumatology, Department of Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania
  • 2Wright Center for Clinical and Translational Research, Virginia Commonwealth University, Richmond
  • 3City Clinical Hospital No. 15 Named After O.M. Filatov, Moscow, Russian Federation
  • 4Maimonides Medical Center, Brooklyn, New York
  • 5University of California, San Francisco, Zuckerberg San Francisco General Hospital, San Francisco
  • 6Boston Medical Center and Boston University School of Medicine, Boston, Massachusetts
  • 7McGovern Medical School at The University of Texas Health Science Center at Houston
  • 8Center of Allergy and Immunology, Clinical City Hospital No. 52, Moscow, Russian Federation
  • 9Department of Allergy and Clinical Immunology, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation, Moscow, Russian Federation
  • 10Therapeutic Department, Aleksandrovskaya Hospital, St Petersburg, Russian Federation
  • 11City Multi-specialty Hospital No. 2, St Petersburg, Russian Federation
  • 12Unidad Medicina Interna, Hospital Universitario Infanta Sofía, Madrid, Spain
  • 13Unidad de Enfermedades Sistémicas Autoinmunes y Minoritarias, Servicio de Medicina Interna, Hospital Ramón y Cajal, Madrid, Spain
  • 14Novartis Pharmaceuticals Corporation, East Hanover, New Jersey
  • 15Novartis Ireland Ltd, Dublin, Ireland
JAMA. 2021;326(3):230-239. doi:10.1001/jama.2021.9508
Key Points

Question  Is the anti–interleukin-1β antibody canakinumab effective to treat patients hospitalized with COVID-19 and hyperinflammation?

Finding  This randomized clinical trial included 454 patients hospitalized with severe COVID-19 not requiring invasive mechanical ventilation (IMV) and with elevated C-reactive protein or ferritin levels. Treatment with intravenous canakinumab vs placebo resulted in survival without IMV at 29 days of 88.8% vs 85.7%, a difference that was not statistically significant.

Meaning  Among patients hospitalized with severe COVID-19, treatment with canakinumab, compared with placebo, did not significantly increase the likelihood of survival without IMV.


Importance  Effective treatments for patients with severe COVID-19 are needed.

Objective  To evaluate the efficacy of canakinumab, an anti–interleukin-1β antibody, in patients hospitalized with severe COVID-19.

Design, Setting, and Participants  This randomized, double-blind, placebo-controlled phase 3 trial was conducted at 39 hospitals in Europe and the United States. A total of 454 hospitalized patients with COVID-19 pneumonia, hypoxia (not requiring invasive mechanical ventilation [IMV]), and systemic hyperinflammation defined by increased blood concentrations of C-reactive protein or ferritin were enrolled between April 30 and August 17, 2020, with the last assessment of the primary end point on September 22, 2020.

Intervention  Patients were randomly assigned 1:1 to receive a single intravenous infusion of canakinumab (450 mg for body weight of 40-<60 kg, 600 mg for 60-80 kg, and 750 mg for >80 kg; n = 227) or placebo (n = 227).

Main Outcomes and Measures  The primary outcome was survival without IMV from day 3 to day 29. Secondary outcomes were COVID-19–related mortality, measurements of biomarkers of systemic hyperinflammation, and safety evaluations.

Results  Among 454 patients who were randomized (median age, 59 years; 187 women [41.2%]), 417 (91.9%) completed day 29 of the trial. Between days 3 and 29, 198 of 223 patients (88.8%) survived without requiring IMV in the canakinumab group and 191 of 223 (85.7%) in the placebo group, with a rate difference of 3.1% (95% CI, −3.1% to 9.3%) and an odds ratio of 1.39 (95% CI, 0.76 to 2.54; P = .29). COVID-19–related mortality occurred in 11 of 223 patients (4.9%) in the canakinumab group vs 16 of 222 (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, 0.30 to 1.50). Serious adverse events were observed in 36 of 225 patients (16%) treated with canakinumab vs 46 of 223 (20.6%) who received placebo.

Conclusions and Relevance  Among patients hospitalized with severe COVID-19, treatment with canakinumab, compared with placebo, did not significantly increase the likelihood of survival without IMV at day 29.

Trial Registration  ClinicalTrials.gov Identifier: NCT04362813