Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jan 26:14:1098703.
doi: 10.3389/fmicb.2023.1098703. eCollection 2023.

Evaluation of anakinra in the management of patients with COVID-19 infection: A randomized clinical trial

Eman Zeyad I Elmekaty  1 , Aya Maklad  2 , Rawan Abouelhassan  2 , Waqar Munir  1 , Mohamed Izham Mohamed Ibrahim  2 , Arun Nair  1 , Rim Alibrahim  1 , Fatima Iqbal  1 , Ahmad Al Bishawi  1 , Alaaeldin Abdelmajid  1 , Mohamed Aboukamar  1 , Hamad Abdel Hadi  1 , Mohammed Abu Khattab  1 , Hussam Al Soub  1 , Muna Al Maslamani  1
Affiliations

Evaluation of anakinra in the management of patients with COVID-19 infection: A randomized clinical trial

Eman Zeyad I Elmekaty et al. Front Microbiol. .

Abstract

Background: The global COVID-19 pandemic led to substantial clinical and economic outcomes with catastrophic consequences. While the majority of cases has mild to moderate disease, minority of patients progress into severe disease secondary to the stimulation of the immune response. The hyperinflammatory state contributes towards progression into multi-organ failure which necessitates suppressive therapy with variable outcomes. This study aims to explore the safety and efficacy of anakinra in COVID-19 patients with severe disease leading to cytokine release syndromes.

Methods: In this open-label, multi-center, randomized clinical trial, patients with confirmed COVID-19 infection with evidence of respiratory distress and signs of cytokine release syndrome were randomized in 1:1 ratio to receive either standard of care (SOC) or anakinra (100 mg subcutaneously every 12 h for 3 days then 100 mg subcutaneously once daily for 4 days) in addition to SOC. The primary outcome was treatment success at day 14 as defined by the WHO clinical progression score of ≤3. Primary analysis was based upon intention-to-treat population, with value of p of <0.05.

Results: Out 327 patients screened for eligibility, 80 patients were recruited for the study. The mean age was 49.9 years (SD = 11.7), with male predominance at 82.5% (n = 66). The primary outcome was not statistically different (87.5% (n = 35) in anakinra group vs. 92.5% (n = 37) in SOC group, p = 0.712; OR = 1.762 (95%CI: 0.39-7.93). The majority of reported adverse events were mild in severity and not related to the study treatment. Elevated aspartate aminotransferase was the only significant adverse event which was not associated with discontinuation of therapy.

Conclusion: In patients with severe COVID-19 infection, the addition of anakinra to SOC treatment was safe but was not associated with significant improvement according to the WHO clinical progression scale. Further studies are warranted to explore patients' subgroups characteristics that might benefit from administered therapy.

Clinical trial registration: Trial registration at ClinicalTrials.gov, identifier: NCT04643678.

Keywords: COVID-19; SARS-CoV-2; anakinra; cytokine release syndrome; interlukin-1 inhibitor; pneumonia.

PubMed Disclaimer

Conflict of interest statement

All authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow diagram.
Figure 2
Figure 2
Change in the WHO clinical progression Score between day 1 and day 14.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Aouba A., Baldolli A., Geffray L., Verdon R., Bergot E., Martin-Silva N., et al. . (2020). Targeting the inflammatory cascade with anakinra in moderate to severe COVID-19 pneumonia: case series. Ann. Rheum. Dis. 79, 1381–1382. doi: 10.1136/annrheumdis-2020-217706, PMID: - DOI - PubMed
    1. Atagündüz P., Keser G., Soy M. (2021). Interleukin-1 inhibitors and vaccination including COVID-19 in inflammatory rheumatic diseases: a nonsystematic review. Front. Immunol. 12:734279. doi: 10.3389/fimmu.2021.734279 - DOI - PMC - PubMed
    1. Audemard-Verger A., Le Gouge A., Pestre V., Courjon J., Langlois V., Vareil M. O., et al. . (2022). Efficacy and safety of anakinra in adults presenting deteriorating respiratory symptoms from COVID-19: a randomized controlled trial. PLoS One 17:e0269065. doi: 10.1371/journal.pone.0269065, PMID: - DOI - PMC - PubMed
    1. Balkhair A., Al-Zakwani I., Al Busaidi M., Al-Khirbash A., Al Mubaihsi S., BaTaher H., et al. . (2021). Anakinra in hospitalized patients with severe COVID-19 pneumonia requiring oxygen therapy: results of a prospective, open-label, interventional study. Int. J. Infect. Dis. 103, 288–296. doi: 10.1016/j.ijid.2020.11.149, PMID: - DOI - PMC - PubMed
    1. Barkas F., Filippas-Ntekouan S., Kosmidou M., Liberopoulos E., Liontos A., Milionis H. (2021). Anakinra in hospitalized non-intubated patients with coronavirus disease 2019: A systematic review and meta-analysis. Rheumatology 60, 5527–5537. doi: 10.1093/rheumatology/keab447, PMID: - DOI - PMC - PubMed

Associated data