An open label trial of anakinra to prevent respiratory failure in COVID-19
- National and Kapodistrian University of Athens, Medical School, Greece
- Democritus University of Thrace, Medical School, Greece
- Aristotle University of Thessaloniki, Medical School, Greece
- National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Greece
- Univeristy of Ioannina School of Medicine, Greece
- University of Ioannina, School of Health Sciences, Faculty of Medicine, Greece
- General Hospital of Kerkyra, Greece
- University of Patras, Greece
- Radboud University Medical Centre, Netherlands
- Copenhagen University Hospital Hvidovre, Denmark
- Radboud University Nijmegen Medical Centre, Netherlands
Abstract
Background It was studied if early suPAR-guided anakinra treatment can prevent severe respiratory failure (SRF) of COVID-19.
Methods 130 patients with suPAR ≥6 ng/ml were assigned to subcutaneous anakinra 100mg once daily for 10 days. Primary outcome was SRF incidence by day 14 defined as any respiratory ratio below 150 mmHg necessitating mechanical or non-invasive ventilation. Main secondary outcomes were 30-day mortality and inflammatory mediators; 28-day WHO-CPS was explored. Propensity-matched standard-of care comparators were studied.
Results 22.3% with anakinra treatment and 59.2% comparators (hazard ratio, 0.30; 95%CI, 0.20-0.46) progressed into SRF; 30-day mortality was 11.5% and 22.3% respectively (hazard ratio 0.49; 95% CI 0.25-0.97). Anakinra was associated with decrease in circulating interleukin (IL)-6, sCD163 and sIL2-R; IL-10/IL-6 ratio on day 7 was inversely associated with SOFA score; patients were allocated to less severe WHO-CPS strata.
Conclusions Early suPAR-guided anakinra decreased SRF and restored the pro-/anti-inflammatory balance.
Trial Registration: ClinicalTrials.gov, NCT04357366
Data availability
Data of this submission are anticipated to be part of a submission package to the European Medicines Agency for the request of approval of Anakinra for the management of COVID-19 guided by the biomarker suPAR. Once this is finalized, the data will be made publicly available upon request. Requests will require signing contract with the sponsor of the study which is the Hellenic Institute for the Study of Sepsis. The responsible official is Ms Leda Efstratiou who is the DPO responsible for GDPR. Interested researchers should contact Ms Efstratiou at le.efstrat@gmail.com and headed@sepsis.gr to request access to the data.
Article and author information
Author details
Evdoxia Kyriazopoulou
Evangelos J Giamarellos-Bourboulis
Funding
Hellenic Institute for the Study of Sepsis (NA)
- Evangelos J Giamarellos-Bourboulis
Technomar Shipping Inc (NA)
- Evangelos J Giamarellos-Bourboulis
Swedish Orphan Biovitrum AB (NA)
- Evangelos J Giamarellos-Bourboulis
Horizon 2020 (RISKinCOVID)
- Evangelos J Giamarellos-Bourboulis
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Arduino A Mangoni, Flinders Medical Centre, Australia
Ethics
Human subjects: Approved in Greece by National Ethics Committee approval 38/20; National Organization for Medicines approval ISO 28/20.Written informed consent was provided by the patient or legal representative before screening.
Version history
- Received: December 29, 2020
- Accepted: March 4, 2021
- Accepted Manuscript published: March 8, 2021 (version 1)
- Version of Record published: April 9, 2021 (version 2)
Copyright
© 2021, Kyriazopoulou et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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An open label trial of anakinra to prevent respiratory failure in COVID-19
eLife 10:e66125.
https://doi.org/10.7554/eLife.66125
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