Systematic review and meta-analysis of anakinra, sarilumab, siltuximab and tocilizumab for COVID-19

  • Thorax. 2021 Sep;76(9):907-919. doi: 10.1136/thoraxjnl-2020-215266.
Fasihul A Khan  1 ,  Iain Stewart  2 ,  Laura Fabbri  2 ,  Samuel Moss  2 ,  Karen Robinson  3 ,  Alan Robert Smyth  4 ,  Gisli Jenkins  2
Affiliations
  • 1. Respiratory Medicine, University of Nottingham, Nottingham, UK [email protected].
  • 2. Respiratory Medicine, University of Nottingham, Nottingham, UK.
  • 3. Johns Hopkins University, Baltimore, Maryland, USA.
  • 4. Division of Child Health, Obstetrics and Gynaecology, University of Nottingham, Nottingham, UK.
PMID: 33579777 DOI: 10.1136/thoraxjnl-2020-215266
Abstract

Background: There is accumulating evidence for an overly activated immune response in severe COVID-19, with several studies exploring the therapeutic role of immunomodulation. Through systematic review and meta-analysis, we assess the effectiveness of specific interleukin inhibitors for the treatment of COVID-19.

Methods: Electronic databases were searched on 7 January 2021 to identify studies of immunomodulatory agents (anakinra, sarilumab, siltuximab and tocilizumab) for the treatment of COVID-19. The primary outcomes were severity on an Ordinal Scale measured at day 15 from intervention and days to hospital discharge. Key secondary endpoints included overall mortality.

Results: 71 studies totalling 22 058 patients were included, 6 were randomised trials. Most studies explored outcomes in patients who received tocilizumab (60/71). In prospective studies, tocilizumab was associated with improved unadjusted survival (risk ratio 0.83, 95% CI 0.72 to 0.96, I2=0.0%), but conclusive benefit was not demonstrated for Other outcomes. In retrospective studies, tocilizumab was associated with less severe outcomes on an Ordinal Scale (generalised OR 1.34, 95% CI 1.10 to 1.64, I2=98%) and adjusted mortality risk (HR 0.52, 95% CI 0.41 to 0.66, I2=76.6%). The mean difference in duration of hospitalisation was 0.36 days (95% CI -0.07 to 0.80, I2=93.8%). There was substantial heterogeneity in retrospective studies, and estimates should be interpreted cautiously. Other immunomodulatory agents showed similar effects to tocilizumab, but insufficient data precluded meta-analysis by agent.

Conclusion: Tocilizumab was associated with a lower relative risk of mortality in prospective studies, but effects were inconclusive for Other outcomes. Current evidence for the efficacy of anakinra, siltuximab or sarilumab in COVID-19 is insufficient, with further studies urgently needed for conclusive findings.

Prospero registration number: CRD42020176375.

Keywords
ARDS; COVID-19; respiratory infection; viral infection.
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