COVID-19 Evidence Alerts
from McMaster PLUSTM

Current best evidence for clinical care (more info)

Treatment Khan FA, Stewart I, Fabbri L, et al. Systematic review and meta-analysis of anakinra, sarilumab, siltuximab and tocilizumab for COVID-19. Thorax. 2021 Feb 12. pii: thoraxjnl-2020-215266. doi: 10.1136/thoraxjnl-2020-215266.

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.


Discipline / Specialty Area Score
Intensivist/Critical Care
Hospital Doctor/Hospitalists
Internal Medicine
Infectious Disease
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Comments from MORE raters

Infectious Disease rater

This is a good review but probably already obsolete.

Infectious Disease rater

The data on immunomodulatory therapy have been confusing with early studies showing no benefit, later studies showing benefit. This systematic review shows that at least for tocilizumab, there are data to support its use.

Internal Medicine rater

The area is evolving so rapidly that any SR published is immediately out of date. There is a large RCT reporting now.

Respirology/Pulmonology rater

A good quality systematic review about the effects of immune-modulating biologics in the treatment of severe COVID-19 infection. A possible mortality benefit is attributed to tocilizumab. Nevertheless, there is no new information that would help or guide me in selecting patients with COVID-19 infection for treatment with tocilizumab or other biologics.