Anakinra in hospitalized non-intubated patients with coronavirus disease 2019: a systematic review and meta-analysis

Barkas, Fotios; Ntekouan, Sebastian Filippas; Kosmidou, Maria; Liberopoulos, Evangelos; Liontos, Angelos; Milionis, Haralampos

BACKGROUND: Acute respiratory distress syndrome and cytokine release syndrome are the major complications of coronavirus disease 2019 (COVID-19) associated with increased mortality risk. OBJECTIVES: We performed a meta-analysis to assess the efficacy and safety of anakinra in adult hospitalized non-intubated patients with COVID-19. SEARCH METHODS: Relevant trials were identified by searching literature until 24 April 2021 using the following terms: anakinra, interleukin 1, coronavirus, COVID-19, SARS-CoV-2. SELECTION CRITERIA: Trials evaluating the effect of anakinra on the need for invasive mechanical ventilation and mortality in hospitalized non-intubated patients with COVID-19. RESULTS: Nine studies (n = 1,119) were eligible for inclusion in the present meta-analysis. Their bias risk with reference to the assessed parameters was high. In pooled analyses, anakinra reduced the need for invasive mechanical ventilation (odds ratio, OR: 0·38, 95% confidence interval, CI: 0·17–0·85, p= 0.02, I(2)=67%; 6 studies, n = 587) and mortality risk (OR: 0·32, 95% CI: 0·23–0·45, p< 0·00001, I(2)=0%; 9 studies, n = 1,119) compared with standard of care therapy. There were no differences regarding the risk of adverse events, including liver dysfunction (OR: 0·75, 95% CI: 0·48–1·16, p> 0·05, I(2)=28%; 5 studies, n = 591) and bacteremia (OR: 1·07, 95% CI: 0·42–2·73, p> 0·05, I(2)=71%; 6 studies, n = 727). CONCLUSIONS: Available evidence shows that treatment with anakinra reduces both the need for invasive mechanical ventilation and mortality risk of hospitalized non-intubated patients with COVID-19 without increasing the risk of adverse events. Confirmation of efficacy and safety requires randomized placebo-controlled trials.