COVID-19 Evidence Alerts
from McMaster PLUSTM

Current best evidence for clinical care (more info)

Treatment Lan SH, Lai CC, Huang HT, et al. Tocilizumab for severe COVID-19: a systematic review and meta-analysis. Int J Antimicrob Agents. 2020 Sep;56(3):106103. doi: 10.1016/j.ijantimicag.2020.106103. Epub 2020 Jul 23.

This systemic review and meta-analysis aimed to assess the efficacy of tocilizumab for the treatment of severe coronavirus disease 2019 (COVID-19). Candidate studies up to 24 May 2020 were identified from PubMed, Cochrane Library, Embase, medRxiv and bioRxiv. Treatment outcomes included mortality, risk of intensive care unit (ICU) admission and the requirement for mechanical ventilation (MV). Seven retrospective studies involving 592 adult patients with severe COVID-19, including 240 in the tocilizumab group and 352 in the control group, were enrolled. All-cause mortality of severe COVID-19 patients among the tocilizumab group was 16.3% (39/240), which was lower than that in the control group (24.1%; 85/352). However, the difference did not reach statistical significance [risk ratio (RR) = 0.62, 95% confidence interval (CI) 0.31-1.22; I2 = 68%]. Additionally, risk of ICU admission was similar between the tocilizumab and control groups (35.1% vs. 15.8%; RR = 1.51, 95% CI 0.33-6.78; I2 = 86%). The requirement for MV was similar between the tocilizumab and control groups (32.4% vs. 28.6%; RR = 0.82, 95% CI 0.14-4.94; I2 = 91%). However, these non-significant differences between the tocilizumab and control groups may have been the result of baseline characteristics of the tocilizumab group, which were more severe than those of the control group. Based on low-quality evidence, there is no conclusive evidence that tocilizumab would provide any additional benefit to patients with severe COVID-19. Therefore, further recommendation of tocilizumab for COVID-19 cases should be halted until high-quality evidence from randomised controlled trials is available.

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

Hospital Doctor/Hospitalists rater

In this meta analysis of severe COVID patient is receiving tocilizumab (an anti-IL-6, currently used for cytokine storm), 7 retrospective studies were identified; death rates ranged from 3 to 38% for all patients; confounders included use of multiple other treatments including hydroxychloroquine, lopinavir and ritonavir, steroid, and “standard of care"not otherwise specified; heterogeneity was extremely large; no statistical differences were seen between arms. In the end, the only way to know whether this works is through a randomized controlled trial; we do not have that level of evidence. Serious bacterial superinfections are a significant risk with this strategy, as we are also seeing locally; unfortunately this study was not able to collate that data because of reporting differences between studies. I do not believe anything here is conclusive enough to change my mind about whether this works or whether benefits outweigh harms.

Intensivist/Critical Care rater

This is outdated since the recent RCT that showed tocilizumab does not have beneficial effects in this setting.

Respirology/Pulmonology rater

Tocilizumab is being used in some cases of COVID. This is a helpful article about this medication.

Respirology/Pulmonology rater

This is a well done meta-analysis of several trials for Tocilizumab vs placebo for treatment of COVID-19 pneumonia. The criteria for meta-analysis selection, inclusion, review and interpretation are well met. The conclusions are within the scope of the reviewed data and the paper is well written. In the era of COVID, there is abundance of poor quality research publications. This is a compilation of several poor quality research studies about use of Tocilizumab vs placebo in patients with COVID19 viral infection/pneumonia. Using the age old adage of "garbage in, garbage out", we can summarize that based on the available data use of Tocilizumab does not appear to have any statistically significant benefit over placebo. The authors have identified all these limitations well.