Real-life use of High-Dose Anakinra in Patients with COVID-19 Treated with Remdesivir

Abstract

Aim: Aim of this study was to evaluate the effect of anakinra (ANK) addition to remdesivir (RDV) on all-cause 28-day mortality in patients hospitalized with COVID-19. Patients & methods: ANK was administered intravenously at a dose of 5 mg/kg every 12 h in patients with severe respiratory failure and pronounced inflammatory status. 58 patients were treated with RDV + ANK, 219 patients with RDV. Results: The estimate of mortality at 28 days was 17.2% in the RDV + ANK group and 21.4% in the RDV group. Median time to death was 14 days in the RDV + ANK group and 19 in the RDV group. Conclusion: Despite severe respiratory failure and pronounced inflammatory status, patients who received RDV + ANK had similar mortality compared with patients who received RDV.

Plain language summary

In this study, we looked at hospitalized patients with COVID-19 pneumonia who were given different treatments. These included a combination therapy, an antiviral medication only or an antiviral and anti-inflammatory. Almost all patients received treatment with corticosteroids, another common anti-inflammatory medication that is currently part of standard COVID-19 treatment. Patients treated with the antiviral and anti-inflammatory showed more severe pneumonia compared with patients who received just the antiviral, probably reflecting the physicians’ choice to give an anti-inflammatory to patients with a more serious clinical condition. Nevertheless, the mortality rate was similar in the two groups. The combination therapy of the antiviral and anti-inflammatory might improve mortality in COVID-19 patients with severe pneumonia to be comparable to mortality in patients with less severe clinical presentations.

Keywords: :

• anakinra
• COVID-19
• mortality
• remdesivir
• SARS-CoV2

Author contributions

Conceptualization and methodology: R Monardo, A Mastrangelo, L Galli, A Castagna, M Ripa, A Tomelleri, C Campochiaro, L Dagna and M Ripa. Software and formal analysis: L Galli, P Cinque, A Castagna and P Scarpellini. Validation and investigation: A Tomelleri, V Spagnuolo, G Cavalli, F Ciceri, R Monardo, C Campochiaro, P Cinque and P Scarpellini. Resources and data curation: A Tomelleri, G Cavalli, L Dagna, C Campochiaro and V Spagnuolo. Writing original draft: R Monardo, M Ripa, L Galli and A Mastrangelo. Writing review and editing: R Monardo, M Ripa, L Galli and C Campochiaro. Visualization and supervision: F Ciceri, M Ripa and L Galli. Project administration: M Ripa, A Castagna, F Ciceri and L Dagna.

Acknowledgments

This work was previously presented as a poster during the 2022 Conference on Retroviruses and Opportunistic Infections (R Monardo, A Mastrangelo, L Galli, et al. Real-life use of high-dose anakinra in COVID-19 207 patients treated with remdesivir [CROI Abstract 302]). In Special Issue: Abstracts From the 2022 Conference on Retroviruses and Opportunistic Infections. Top Antiv. Med. (2022). The authors thank all colleagues of the Infectious Disease Department and all workers on the frontline during the COVID-19 pandemic.

Financial disclosure

The authors have no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Competing interests disclosure

A Castagna has received consultancy payments and speaking fees from Bristol-Myers Squibb, Gilead, ViiV Healthcare, Merck Sharp & Dohme and Janssen-Cilag. G Cavalli and L Dagna have received consultation honoraria from Sobi, Roche and Sanofi outside the submitted work. C Campochiaro has received consultation honoraria from Roche outside the submitted work. The authors have no other competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval from the hospital ethics committee (protocol no. 34/int/2020) and have followed the principles of the Declaration of Helsinki. Informed consent was obtained from all patients. This study was registered on ClinicalTrials.gov (NCT04318366).