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.