Trial results do not support canakinumab for COVID-19
medwireNews: Treatment with the interleukin (IL)-1β inhibitor canakinumab does not improve the likelihood of survival without invasive mechanical ventilation (IMV) among hospitalized patients with severe COVID-19 and systemic hyperinflammation, suggest findings from the CAN-COVID trial.
The phase 3 study “was initiated based on the premise that IL-1 inhibition had previously been shown to inhibit inflammatory response in patients with systemic hyperinflammation and cytokine storm in conditions such as macrophage activation syndrome,” and it was hypothesized that canakinumab “would decrease the release of cytokines in patients with severe COVID-19 pneumonia,” explain the investigators in JAMA.
“Early during the pandemic and at the time of study design, the results of case-control studies with the IL-1 blocker anakinra further supported this hypothesis,” they add.
For the trial, 446 hospitalized patients from 39 centers in Europe and the USA with COVID-19 pneumonia, systemic inflammation, and hypoxia not requiring IMV were randomly assigned to receive a single intravenous infusion of canakinumab (450–750 mg based on bodyweight) or placebo alongside local standard care.
Roberto Caricchio (Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, USA) and co-investigators report that the proportion of patients who were alive and did not require IMV at any time between day 3 and 29 was comparable in the canakinumab and placebo arms, at 88.8% and 85.7%, respectively.
There was also no significant difference in COVID-19 mortality rates by day 29 among participants treated with canakinumab versus placebo (4.9 vs 7.2%).
A total of 54.2% and 53.8% of patients in the canakinumab and placebo arms, respectively, experienced adverse events (AEs), and the corresponding rates of serious AEs were 16.0% and 20.6%.
“Most AEs until day 29 were considered to be related to the underlying condition and not related to study drug,” say Caricchio and team.
They note that the CAN-COVID trial had a number of limitations, such as evolving standard-of-care treatment during the time the study was carried out and an imbalance in glucocorticoid use across the two study arms. The investigators also point out that “mortality and morbidity outcomes continued to become increasingly more favorable” during the course of the pandemic.
“These challenges underscore the difficulty in conducting randomized clinical trials in the changing treatment approach during the COVID-19 pandemic,” and the “shortcomings may be best addressed in the future by event-driven trial designs,” they conclude.
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2021 Springer Healthcare Ltd, part of the Springer Nature Group
23 July 2021: The coronavirus pandemic is affecting all healthcare professionals across the globe. Medicine Matters’ focus, in this difficult time, is the dissemination of the latest data to support you in your research and clinical practice, based on the scientific literature. We will update the information we provide on the site, as the data are published. However, please refer to your own professional and governmental guidelines for the latest guidance in your own country.