Following a well-earned break, the Taskforce team has now returned to full capacity. Global evidence surveillance continued throughout January, with six clinical panel meetings held since January 11. We look forward to continuing to keep Australian clinicians armed with the latest evidence-based guidance for the treatment of people with COVID-19.
Taskforce recommendation for tocilizumab unchanged
The Taskforce Disease Modifying Treatments and Chemoprophylaxis Panel and the Guidelines Leadership Group have incorporated the results of the tocilizumab arm of the REMAP-CAP trial (published as a pre-print on January 7, 2021) into the body of evidence underpinning the Taskforce’s recommendation on the use of tocilizumab. There remains uncertainty whether tocilizumab is more effective and safer than standard care in treating patients with COVID-19. As a result, the guidance remains unchanged and the Taskforce recommends that tocilizumab is only used in the treatment of COVID-19 in the context of randomised trials.
The REMAP-CAP preliminary results (yet to be peer reviewed) suggest a mortality benefit in patients with critical illness who were receiving respiratory or cardiovascular organ support. These data contrast with the pre-existing meta-analysis of five randomised trials conducted by the Taskforce, in which a mortality benefit was not observed in patients using tocilizumab. Importantly, the vast majority of relevant data published before REMAP-CAP focused on patients with moderate to severe illness, with the exception of the COVACTA trial which included 108 patients with critical illness.
To determine whether the apparent differences in effect on mortality might be explained by differences in disease severity, the Taskforce assessed the credibility of these subgroups using the Instrument to assess the Credibility of Effect Modification Analyses (ICEMAN).
This analysis indicates that it is likely to be inappropriate to analyse data in subgroups based on disease severity. The full ICEMAN analysis can be found here.
With the incorporation of data from the REMAP-CAP trial into the tocilizumab meta-analysis, the Taskforce identified a trend towards benefit, but uncertainty remains.
The Taskforce is awaiting the expected peer-reviewed publication of these data, the publication of the tocilizumab arm of the RECOVERY trial, and is currently reviewing another study comparing tocilizumab with standard care in adults receiving supplemental oxygen or mechanical ventilation (Veiga et al. BMJ doi: 10.1136/bmj.n84).
Recommendations regarding the use of tocilizumab will be updated as appropriate in future versions of the guidelines.
Azithromycin recommendation updated to Do Not Use
The Taskforce has updated the azithromycin recommendation to include recently published data from the RECOVERY trial, which included over 7,700 patients with mild to critical COVID-19 illness. Results demonstrated no difference in mortality or requirement of mechanical ventilation/ECMO in patients treated with azithromycin compared to those receiving standard care. The Taskforce has revised the previous guidance advising that azithromycin should only be used to treat COVID-19 in the context of randomised trials, to recommending that azithromycin is not used to treat COVID-19.
Further details about these recommendations are below.
COVID-19 research pipeline
Do not use baricitinib for the treatment of COVID-19 outside of randomised trials with appropriate ethical approval.
Do not use REGN-COV2 for the treatment of COVID-19 outside of randomised trials with appropriate ethical approval.
Do not use sarilumab for the treatment of COVID-19 outside of randomised trials with appropriate ethical approval.
The evidence base has been updated and the recommendation has been changed from ‘do not use outside of randomised trials’ to ‘do not use’.
The evidence base has been updated with no change to the strength or direction of the recommendation.
Text has been added to the ‘Remark’ section of the recommendation regarding the recent statement from chief investigators of the RECOVERY trial.
The Taskforce is continually monitoring research to update recommendations as new evidence accumulates.
11 clinical flowcharts have been developed by the Taskforce to cover:
Changes to flowcharts this week include:<
We are currently reviewing evidence to develop recommendations and flowcharts to guide practice in areas including:
Since late December Cochrane has published:
The full list of Cochrane Reviews and related content from the Cochrane Library relating to the COVID-19 pandemic can be found here.
It is a core mission of the Taskforce to engage with frontline clinicians to rapidly identify and address priority clinical questions.
Each week we collect suggestions for new clinical questions or topics for consideration by the Taskforce. A document that lists all of the suggested questions, topics and new patient groups that we have received to date is available here.
Please encourage your clinical colleagues to provide their insights via the website.