TY  - JOUR
PB  - SPRINGER
N2  - PURPOSE: 
Interleukin-6 (IL-6) levels discriminate between patients with mild and severe COVID-19, making IL-6 inhibition an attractive therapeutic strategy. We conducted a systematic review, meta-analysis, trial sequential analysis (TSA), and meta-regression of randomized-controlled trials to ascertain the benefit of IL-6 blockade with tocilizumab for COVID-19.

METHODS:

We included randomized-controlled trials (RCTs) allocating patients with COVID-19 to tocilizumab. Our control group included standard care or placebo. Trials co-administering other pharmacological interventions for COVID-19 were not excluded. Primary outcome was 28?30 day mortality. Secondary outcomes included progression-to-severe disease defined as need for mechanical ventilation, intensive-care unit (ICU) admission, or a composite.

RESULTS: We identified 10 RCTs using tocilizumab, 9 of which reported primary outcome data (mortality), recruiting 6493 patients with 3358 (52.2%) allocated to tocilizumab. Tocilizumab may be associated with an improvement in mortality (24.4% vs. 29.0%; OR 0.87 [0.74?1.01]; p?=?0.07; I2?=?10%; TSA adjusted CI 0.66?1.14). Meta-regression suggested a relationship between treatment effect and mortality risk, with benefit at higher levels of risk (logOR vs %risk beta?=??0.018 [?0.037 to ?0.002]; p?=?0.07). Tocilizumab did reduce the need for mechanical ventilation and was associated with a benefit in the composite secondary outcome but did not reduce ICU admission.

CONCLUSIONS:
For hospitalized COVID-19 patients, there is some evidence that tocilizumab use may be associated with a short-term mortality benefit, but further high-quality data are required. Its benefits may also lie in reducing the need for mechanical ventilation.
ID  - discovery10130588
KW  - COVID-19
KW  -  
Immunologic factors
KW  -  
Interleukin-6
KW  -  
Meta-analysis
AV  - public
Y1  - 2021/06//
EP  - 652
TI  - Tocilizumab in COVID-19: a meta-analysis, trial sequential analysis, and meta-regression of randomized-controlled trials
UR  - https://doi.org/10.1007/s00134-021-06416-z
A1  - Snow, TAC
A1  - Saleem, N
A1  - Ambler, G
A1  - Nastouli, E
A1  - Singer, M
A1  - Arulkumaran, N
JF  - Intensive Care Medicine
VL  - 47
SP  - 641
IS  - 6
N1  - This version is the author accepted manuscript. For information on re-use, please refer to the publisher?s terms and conditions.
ER  -