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Respiratory infection
Original research
Systematic review and meta-analysis of anakinra, sarilumab, siltuximab and tocilizumab for COVID-19
  1. Fasihul A Khan1,
  2. Iain Stewart1,
  3. Laura Fabbri1,
  4. Samuel Moss1,
  5. Karen Robinson2,
  6. Alan Robert Smyth3,
  7. Gisli Jenkins1
  1. 1 Respiratory Medicine, University of Nottingham, Nottingham, UK
  2. 2 Johns Hopkins University, Baltimore, Maryland, USA
  3. 3 Division of Child Health, Obstetrics and Gynaecology, University of Nottingham, Nottingham, UK
  1. Correspondence to Dr Fasihul A Khan, Centre for Respiratory Research, University of Nottingham, Nottingham NG7 2RD, UK; fasihul.khan{at}nottingham.ac.uk

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.

  • viral infection
  • respiratory infection
  • ARDS
  • COVID-19

Data availability statement

Data sharing not applicable as no datasets were generated and/or analysed for this study.

This article is made freely available for use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.

https://bmj.com/coronavirus/usage

https://doi.org/10.1136/thoraxjnl-2020-215266

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    Data availability statement

    Data sharing not applicable as no datasets were generated and/or analysed for this study.

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    Footnotes

    • Contributors FAK, IS and GJ conceived the study. FAK drafted the manuscript, performed the searches and collected the data. LF and SM verified the searches and extracted data. Analysis was performed by FAK and IS. All authors edited and approved the final version before submission.

    • Funding FAK, LF, IS and ARS were supported by the Nottingham National Institute for Health Research (NIHR) Biomedical Research Centre. GJ was supported by an NIHR Research Professorship (RP-2017-08-ST2-014).

    • Competing interests GJ received grants from GlaxoSmithKline, during the conduct of the study, Astra Zeneca, Biogen and Galecto; personal fees from Boehringer Ingelheim, Daewoong, Galapagos, Heptares, Promedior and Roche; non-financial support from NuMedii and Redx; grants and personal fees from Pliant and other supports from Action for Pulmonary Fibrosis, outside the submitted work.

    • Provenance and peer review Not commissioned; externally peer reviewed.