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Tocilizumab for treating COVID-19: a systemic review and meta-analysis of retrospective studies.

ABSTRACT: OBJECTIVES:COVID-19 has become a global epidemic, and effective therapies have not been discovered up to now. We conducted this study to explore the effectiveness and safety of tocilizumab recently used for treating COVID-19. METHOD:A comprehensive search was conducted (up to September 27, 2020), and 19 eligible records were identified according to the inclusion and exclusion criteria. The data of the studies were extracted by 2 independent reviewers and were analyzed to evaluate the safety and availability of tocilizumab for treating COVID-19. RESULTS:Thirteen retrospective case-control studies (n =?2285 patients) and 6 retrospective single-armed studies (n =?208) were retrieved in this study. In the comparison of tocilizumab treatment group (TCZ) and standard treatment group (ST), significant associations with a lower risk of admission to ICU, use of ventilation, and mortality (OR, 95% CI: 0.53, 0.26~1.09; 0.66, 0.46~0.94; 0.44, 0.36~0.55) were found in the tocilizumab treatment group. What is more, patients treated with tocilizumab had better clinical improvement compared with the patients treated with ST (OR, 1.24; 95% CI, 0.96~1.62). After taking tocilizumab, the patients had lower C-reactive protein (CRP), white blood cell count (WBC), aspartate aminotransferase (AST) (WMD, 95% CI: -?99.66, -?156.24~-?43.09; -?0.95, -?1.8~-?0.11; -?12.58, -?18.88~-6.29) but higher troponin (WMD, 7.61; 95% CI, 3.06~12.15) than before. In addition, tocilizumab did not have significant influence on patients' neutrophil count (Neut), lymphocyte count (Lymp), platelet count (Plt), alanine aminotransferase (ALT), and creatine (WMD, 95% CI: -?0.29, -?2.91~2.33; 0.42, -?0.23~1.07; 5.2, -?2.85~13.25; 22.49, -?2.73~47.7; -?44.78, -?93.37~3.81). CONCLUSION:Tocilizumab may have potential effectiveness to treat COVID-19 according to the results of this study. However, more large-scale studies are needed for more accurate conclusions.

SUBMITTER: Zhao M

PROVIDER: S-EPMC7553373 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Tocilizumab for treating COVID-19: a systemic review and meta-analysis of retrospective studies.

Zhao Meng M Lu Jieyu J Tang Yihu Y Dai Yawei Y Zhou Jingxin J Wu Yanhu Y

European journal of clinical pharmacology 20201013 3

<h4>Objectives</h4>COVID-19 has become a global epidemic, and effective therapies have not been discovered up to now. We conducted this study to explore the effectiveness and safety of tocilizumab recently used for treating COVID-19.<h4>Method</h4>A comprehensive search was conducted (up to September 27, 2020), and 19 eligible records were identified according to the inclusion and exclusion criteria. The data of the studies were extracted by 2 independent reviewers and were analyzed to evaluate ...[more]

PMID: 33051695

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Project description:Background and objectives A flare-up in coronavirus disease 2019 (COVID-19) cases threatens the health of people, and though there is no proven pharmacological treatment, many analytical studies have suggested that interleukin-6 (IL-6) levels are elevated in cases of severe COVID-19 and that the anti-IL-6 biologic agent tocilizumab may be beneficial. This is a critical review of studies aiming to assess the safety and efficacy of tocilizumab as compared to the standard regimen in patients with COVID-19. Materials and methods Online databases (PubMed and Cochrane) were searched until June 29, 2020, for original articles investigating the immunological response in COVID-19 and its treatment with tocilizumab. Data on multiple baseline characteristics and pre-specified endpoints were extracted and pooled using a random effect model. We used Review Manager version 5.3 (The Nordic Cochrane Centre, The Cochrane Collaboration, 2014, Denmark) and Stata 11.0 (Stata Corporation LP, College Station, TX) for all analyses. Risk ratios (RR) and the weighted mean difference (WMD) with the corresponding 95% confidence interval (CI) were calculated. Results From a total of 1,246 identified articles, 13 studies were included after duplicate removal and narrowing based on title and abstract. Of the 13 included studies, seven case-control studies were shortlisted for meta-analysis (quantitative) and six-single arm studies were used in the discussion (qualitative). These studies had 766 patients (351 in the tocilizumab arm and 414 in the control arm). Their pooled analysis demonstrated that mortality was significantly lower in the tocilizumab group (RR=0.56 [0.34, 0.92]; p=0.02; I2=76%), as was the need for artificial invasive ventilation (RR=0.34 [0.12, 0.99]; p=0.05; I2=0%) as compared to the control group. No significant differences were observed between tocilizumab and control group in intensive care unit admissions (RR=0.73 [0.15, 3.59]; p=0.70; I2=60%) and risks of post-drug infection (RR=1.29 [0.41, 4.04]; p=0.66; I2=88%). In terms of efficacy outcome, improved oxygen saturation (RR=1.13 [1.04, 1.65]; p=0.02; I2=0%) was reported to be markedly significant in tocilizumab patients when compared with the standard care group. Conclusions Our results based on pooled studies show tocilizumab to be safe and efficacious in reducing mortality among critically ill COVID-19 patients. However, due to the limited number of observational studies, the positive findings should be viewed cautiously and warrant further investigation.

Project description:ObjectivesCytokine release syndrome with elevated interleukin-6 (IL-6) levels is associated with multiorgan damage and death in severe coronavirus disease 2019 (COVID-19). Our objective was to perform a living systematic review of the literature concerning the efficacy and toxicity of the IL-6 receptor antagonist tocilizumab in COVID-19 patients.MethodsData sources were Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Web of Science, Scopus up, preprint servers and Google up to October 8, 2020. Study eligibility criteria were randomized controlled trials (RCTs) and observational studies at low or moderate risk of bias. Participants were hospitalized COVID-19 patients. Interventions included tocilizumab versus placebo or standard of care. We pooled crude risk ratios (RRs) of RCTs and adjusted RRs from cohorts, separately. We evaluated inconsistency between studies with I2. We assessed the certainty of evidence using the GRADE approach.ResultsOf 1156 citations, 24 studies were eligible (five RCTs and 19 cohorts). Five RCTs at low risk of bias, with 1325 patients, examined the effect of tocilizumab on short-term mortality; pooled RR was 1.09 (95%CI 0.80-1.49, I2 = 0%). Four RCTs with 771 patients examined the effect of tocilizumab on risk of mechanical ventilation; pooled RR was 0.71 (95%CI 0.52-0.96, I2 = 0%), with a corresponding number needed to treat of 17 (95%CI 9-100). Among 18 cohorts at moderate risk of bias with 9850 patients, the pooled adjusted RR for mortality was 0.58 (95%CI 0.51-0.66, I2 = 2.5%). This association was observed over all degrees of COVID-19 severity. Data from the RCTs did not show a higher risk of infections or adverse events with tocilizumab: pooled RR 0.63 (95%CI 0.38-1.06, five RCTs) and 0.83 (95%CI 0.55-1.24, five RCTs), respectively.ConclusionsCumulative moderate-certainty evidence shows that tocilizumab reduces the risk of mechanical ventilation in hospitalized COVID-19 patients. While RCTs showed that tocilizumab did not reduce short-term mortality, low-certainty evidence from cohort studies suggests an association between tocilizumab and lower mortality. We did not observe a higher risk of infections or adverse events with tocilizumab use. This review will continuously evaluate the role of tocilizumab in COVID-19 treatment.

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Tocilizumab for treating COVID-19: a systemic review and meta-analysis of retrospective studies.

Publications

Tocilizumab for treating COVID-19: a systemic review and meta-analysis of retrospective studies.

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