key: cord-0723167-6b7ll000
authors: Richier, Quentin; Plaçais, Léo; Lacombe, Karine; Hermine, Olivier
title: Tocilizumab in COVID-19: Give it time!
date: 2021-01-30
journal: Clin Infect Dis
DOI: 10.1093/cid/ciab081
sha: 045165fe9db5133148ec14a20397ae1e5712381b
doc_id: 723167
cord_uid: 6b7ll000

nan

A c c e p t e d M a n u s c r i p t Dear Editor, We read with interest the article by Malgie et al. [1] . Even if we agree with Tleyjeh et al, who discuss the methodology of this article, we believe that the title "a rapid systematic review and meta-analysis" announced clearly an exploratory analysis. Contrariwise, we think that the correspondence by Huang et al. [7] , in which the meta-analysis of five randomized controlled trials (RCTs) [2] [3] [4] [5] [6] did not show a better survival in COVID-19 patients treated by tocilizumab (TCZ), should be more nuanced. Indeed, a superficial analysis could misinform practicians in their therapeutic choice concerning tocilizumab. Here we want to pinpoint the impact of tocilizumab on mortality rate in COVID-19. to their inclusion criteria, because the mortality rate in these latest studies were respectively 1.6 % and 4.9% [5, 6] .

Second, talking about the impact of TCZ on mortality must not overshadow results from retrospective studies when their methodologies are strong. In the metanalysis of 18 cohorts at moderate risk of bias, including 9850 patients, the corrected pooled adjusted RR for mortality was 0.77 (95% CI 0.63-0.95, I 2 =41%), and this association was found in all stage of severity of the disease [8] .

Third, more precise analysis is necessary concerning the results from RCTs because of heterogenous population. For example, in COVACTA sub group of patients who had oxygen, the risk of ventilation or death was significantly reduced (29% vs 42 %) with HR 0.61 (CI 95% : 0.40-0.94 ; p=0.03) [3] . Moreover, in EMPACTA, which included homogenized population who had oxygen, the risk of ventilation or death was significantly reduced by 44 % (12.2% vs 19.3%), HR 0.56 (CI 95% : 0.32 -0.97 ; p=0.035) [2] . In addition, most of the studies evaluate mortality at day 28, and the reduction of the rate of mechanical ventilation may translate in an improvement of mortality after day 28. TCZ is not a magic bullet but in our case, where antiviral drugs seems to have little or no effect, it is important to let time to TCZ, which is, as Huang et al. recalls, well tolerated [7, 9] .

Dr. Lacombe reports personal fees and non-financial support from Gilead, personal fees and non-financial support from MSD, personal fees and non-financial support from Janssen, personal fees and non-financial support from ViiV Healthcare and Abbvie, outside the submitted work. None of the other authors has any potential conflicts.

Decreased mortality in COVID-19 patients treated with Tocilizumab: a rapid systematic review and meta-analysis of observational studies

Roche's phase III EMPACTA study showed Actemra/RoActemra reduced the likelihood of needing mechanical ventilation in hospitalised patients with COVID-19 associated pneumonia

Roche provides an update on the phase III COVACTA trial of Actemra/RoActemra in hospitalised patients with severe COVID-19 associated pneumonia

Tocilizumab in adults hospitalized with moderate oe severe COVID-19 pneumonia: an openlabel randomized controlled trial

Effect of Tocilizumab vs Standard Care on Clinical Worsening in Patients Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial

Efficacy of Tocilizumab in Patients Hospitalized with Covid-19

The impact of tocilizumab on the mortality of patients with COVID-19

Efficacy and safety of tocilizumab in COVID-19 patients: A living systematic review and meta-analysis

Repurposed Antiviral Drugs for Covid-19 -Interim WHO Solidarity Trial Results

A c c e p t e d M a n u s c r i p t