Anakinra treatment in critically ill COVID-19 patients: a prospective cohort study

Abstract

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.

Neutrophils in COVID-19

“…Further, the aforementioned Navarixin, together with other CXCR2 inhibitors, has been proposed as treatment for COVID-19 (95). Another opportunity to block neutrophil hyperactivation is acting on IL-1b/IL-1R interaction; anakinra (IL-1R inhibitor) is currently under clinical investigation showing promising preliminary results (96)(97)(98)(99), whereas canakinumab (IL-1b inhibitor) failed to ameliorate the outcome of severe COVID-19 patients (https:// www.novartis.com/news/media-releases/novartis-provides-updatecan-covid-trial-hospitalized-patients-covid-19-pneumonia-andcytokine-release-syndrome-crs). The complement C5a-C5aR1 interaction also appears to be a candidate in the modulation of neutrophil-induced tissue damage (100).…”

Fast recovery of cardiac function in PIMS-TS patients early using intravenous anti-IL-1 treatment

“…We read with interest the manuscript entitled “Anakinra treatment in critically ill COVID-19 patients: a prospective cohort study” by Kooistra et al [ 1 ] reporting the potential efficacy of anakinra (ANA) to control the hyperinflammation in COVID-19 patients.…”

Tissue Integrity and COVID-19

“…Clinical efficacy of anakinra in severely ill COVID-19 patients has been suggested. Decrease of hyperinflammation as a result of treatment with anakinra was recently reported [41]. Anakinra inhibits both IL-1α and IL-1β.…”