Anakinra treatment in critically ill COVID-19 patients: a prospective cohort study
Open accessAbstract
Background: A subset of critically ill COVID-19 patients develop a hyperinflammatory state. Anakinra, a recombinant interleukin-1 receptor antagonist, is known to be effective in several hyperinflammatory diseases. We investigated the effects of anakinra on inflammatory parameters and clinical outcomes in critically ill, mechanically ventilated COVID-19 patients with clinical features of hyperinflammation. Methods: In this prospective cohort study, 21 critically ill COVID-19 patients treated with anakinra were compared to a group of standard care. Serial data of clinical inflammatory parameters and concentrations of multiple circulating cytokines were determined and aligned on start day of anakinra in the treatment group, and median start day of anakinra in the control group. Analysis was performed for day − 10 to + 10 relative to alignment day. Clinical outcomes were analyzed during 28 days. Additionally, three sensitivity analyses were performed: (1) using propensity score-matched groups, (2) selecting patients who did not receive corticosteroids, and (3) using a subset of the control group aimed to match the criteria (fever, elevated ferritin) for starting anakinra treatment. Results: Baseline patient characteristics and clinical parameters on ICU admission were similar between groups. As a consequence of bias by indication, plasma levels of aspartate aminotransferase (ASAT) (p = 0.0002), ferritin (p = 0.009), and temperature (p = 0.001) were significantly higher in the anakinra group on alignment day. Following treatment, no relevant differences in kinetics of circulating cytokines were observed between both groups. Decreases of clinical parameters, including temperature (p = 0.03), white blood cell counts (p = 0.02), and plasma levels of ferritin (p = 0.003), procalcitonin (p = 0.001), creatinine (p = 0.01), and bilirubin (p = 0.007), were more pronounced in the anakinra group. No differences in duration of mechanical ventilation or ICU length of stay were observed between groups. Sensitivity analyses confirmed these results. Conclusions: Anakinra is effective in reducing clinical signs of hyperinflammation in critically ill COVID-19 patients. A randomized controlled trial is warranted to draw conclusion about the effects of anakinra on clinical outcomes.
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Smaller studies have reported that anakinra, which targets IL-1, may be beneficial.
“This might be similarly true for targeting IL-1 with anakinra for which several smaller studies were reporting beneficial effects (Iglesias-Julián et al., 2020; Kooistra et al., 2020)”
From COVID-19 and the human innate immune system (2021) · cites this paper as Kooistra et al., 2020
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- Authors
- the RCI-COVID-19 Study Group, Kooistra, E. J., Waalders, N. J. B., Grondman, I., Janssen, N. A. F., de Nooijer, A. H., Netea, M. G., van de Veerdonk, F. L., Ewalds, E., van der Hoeven, J. G., Kox, M., & Pickkers, P.
- Affiliations
- Radboud University Medical Center (NL)
- University of Bonn (DE)
- Corresponding author
- Pickkers, Peter
- ORCID
- Venue
- Critical Care
- Published
- 2020-12
- Volume
- 24
- Issue
- 1
- Pages
- 688-688
- ISSN
- 1364-8535 (ISSN-L)
- PMC
- PMC7726611
- OpenAlex
- W3112686683
- Cited by
- 119
- References
- 19
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 8 · 2023: 21 · 2022: 34 · 2021: 50
- FWCI
- 3.44
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Critical Care (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Pure Amsterdam UMC (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- H2020 European Research Council (833247)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- Radboud Universitair Medisch Centrum
- Topics
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Respiratory Support and Mechanisms
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Keywords
- anakinra, COVID-19 pandemic, hyperinflammation, interleukin-1 receptor antagonist, critically ill patients, mechanical ventilation, cytokines, ferritin, procalcitonin, inflammatory markers, clinical outcomes
- MeSH terms
- COVID-19, COVID-19 Drug Treatment, Aged, Female, Humans, Male, Middle Aged, Prospective Studies, Cohort Studies, Critical Illness, Receptors, Interleukin-1, Statistics, Nonparametric, Interleukin 1 Receptor Antagonist Protein, Pandemics
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