key: cord-0765800-ewk71v7s
authors: Huang, Yu-Tien; Chao, Chien-Ming; Lai, Chih-Cheng
title: The impact of tocilizumab on the mortality of patients with COVID-19
date: 2020-11-17
journal: Clin Infect Dis
DOI: 10.1093/cid/ciaa1738
sha: 1480cc8f5742cb3040f0d9e3640caa9916bb9f0d
doc_id: 765800
cord_uid: ewk71v7s

nan

A c c e p t e d M a n u s c r i p t Dear Editor, We read with great interest the meta-analysis by Malgie et al [1] , which showed that mortality was 12% lower for COVID-19 patients treated with tocilizumab compared to COVID-19 patients who were not treated with tocilizumab. Although this is an encouraging finding during COVID-19 pandemic, this finding was based on a meta-analysis of observational studies and required further confirmation by randomized controlled trials (RCTs). Recently, several RCTs [2] [3] [4] investigating the usefulness of tocilizumab for severe COVID-19 patients has been published. However, the findings of these studies seems controversial [5] . Stone et al's study showed tocilizumab was not effective for preventing death in moderately ill hospitalized patients with COVID-19 [2] , but Hermine et al found that tocilizumab may reduce death by day 14 but not mortality by day 28 [3] . Therefore, we did a meta-analysis of these RCTs to provide an update data to clarify one critical issuethe impact of tocilizumab on the mortality of severe COVID-19 patients.

RCTs that compared the clinical efficacy of tocilizumab and other alternative agents or placebo in the treatment of COVID-19 patients were identified through a systematic search of the PubMed until October 22 2020. The results of 28-or 30-day mortality were extracted for the analysis of primary outcome. In addition, the risk of adverse events (AEs), particularly serious infection was collected as secondary outcomes. All statistical analyses were performed using Review Manager (RevMan) version 5.3.

Overall, five RCTs [2-4, 6, 7] fulfilled the inclusion criteria and were included in this meta-analysis.

A total of 1310 patients were enrolled in this study, including 827 and 483 patients received tocilizumab and comparator, respectively. The 28-or 30-day mortality among tocilizumab was 11.97% (n = 99), which was similar to those among control group (10.35%, n = 50). No significant difference was found between these two groups in the pooled analysis of 5 RCTs RCTs [2-4, 6, 7] .

In contrast to Malgie et al's finding [1] , this study did not find the additional mortality benefit of tocilizumab for COVID-19 patients. Our findings were supported by stronger evidence than previous meta-analyses [1, 8] due to the following reasons. First, our finding was based on the meta-analysis of RCTs with low heterogeneity. Second, in the leave one out sensitivity analysis, no single study had a substantial influence on the mortality analysis. Therefore, before further data of ongoing RCTs, our findings indicated that the impact of tocilizumab on the mortality of COVID-19 patients was minimal.

Regarding another concern of risk of tocilizumab associated infection, our finding was consistent with Malgie et al's finding [1] . The risk of serious infection among tocilizumab group was similar to those in the control group. In addition, no significant difference regarding the risk of serious AE was observed between tocilizumab and control group. Thus, it should suggest that tocilizumab would be a safety agent in the treatment of COVID-19 patients.

In conclusion, tocilizumab does not provide mortality benefit for severe COVID-19 patients but it is as tolerable as other comparators. Further recommendation of tocilizumab for COVID-19 patients should therefore be wait until more evidence from ongoing RCTs.

None of the authors has any potential conflicts.

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