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

Abstract

Abstract Objectives Acute respiratory distress syndrome and cytokine release syndrome are the major complications of coronavirus disease 2019 (COVID-19) associated with increased mortality risk. We performed a meta-analysis to assess the efficacy and safety of anakinra in adult hospitalized non-intubated patients with COVID-19. Methods Relevant trials were identified by searching literature until 24 April 2021 using the following terms: anakinra, IL-1, coronavirus, COVID-19, SARS-CoV-2. Trials evaluating the effect of anakinra on the need for invasive mechanical ventilation and mortality in hospitalized non-intubated patients with COVID-19 were included. Results Nine studies (n = 1119) 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% CI: 0.17–0.85, P = 0.02, I2 = 67%; six studies, n = 587) and mortality risk (OR: 0.32, 95% CI: 0.23–0.45, P < 0.00001, I2 = 0%; nine studies, n = 1119) 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, I2 = 28%; five studies, n = 591) and bacteraemia (OR: 1.07, 95% CI: 0.42–2.73, P > 0.05, I2 = 71%; six 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.