Effect of Tocilizumab in Reducing the Mortality Rate in COVID-19 Patients: A Systematic Review with Meta-Analysis.
Ontology highlight
ABSTRACT:
SUBMITTER: Conti V
PROVIDER: S-EPMC8307114 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundIn the absence of highly effective antiviral therapies against SARS-CoV-2, it is crucial to counter the known pathophysiological causes of severe COVID-19. Evaluating the efficacy existing drugs may expedite the development of such therapeutics. Severe COVID-19 is largely the result of a dysregulated immune response characterized by lymphocytopenia, neutrophilia and critical hypercytokinemia, or "cytokine storm," which is largely mediated by the cytokine interleukin-6 (IL-6). The IL-6 inhibitor tocilizumab (TCZ) could potentially suppress the effects of the pro-inflammatory cytokine and thereby lower mortality from the disease. This systematic analysis aimed to investigate and synthesize existing evidence for the efficacy of TCZ in reducing COVID-19 mortality.MethodologyPubMed and SearchWorks searches were performed to locate clinical studies with primary data on TCZ treatment for severe COVID-19. Sixteen case-control studies comparing mortality between TCZ and standard of care (SOC) were identified for quantitative synthesis. The systematic analysis was pre-approved through PROSPERO (CRD42020193479).ResultsCombined mortality for the TCZ-treated and SOC groups were 26.0% and 43.4% respectively. In all but one of the studies, the odds ratio of mortality from COVID-19 pointed towards lower fatality with TCZ vs the SOC. A combined random effects odds ratio calculation yielded an odds ratio of 0.453 (95% CI [0.376-0.547], p < 0.001). Additionally, 18 uncontrolled trials were identified for qualitative analysis producing a raw combined mortality rate of 16.0%.ConclusionsImportant caveats to this research include the lack of prospective randomized control trials and the absence of data from the large COVATA study from the published literature. However, results from this systematic analysis of published research provide positive evidence for the potential efficacy of TCZ to treat severe COVID-19, validating the ethical basis and merit of ongoing randomized controlled clinical trials.
| S-EPMC7643559 | biostudies-literature
Project description:ObjectivesThis systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to investigate the clinical efficacy and safety of tocilizumab for treating patients with COVID-19.MethodsThe PubMed, Embase, Cochrane Library, Clinicaltrials.gov, WHO International Clinical Trials Registry Platform and the preprint server of medRxiv.org were searched from their inception to February 20, 2021. Only RCTs that compared the treatment efficacy and safety of tocilizumab with the placebo or the standard of care for adult patients with COVID-19 were included in this meta-analysis. The primary outcome was 28-day mortality.ResultsThis meta-analysis included eight RCTs which enrolled a total of 6314 patients for randomization, in which 3267 and 3047 patients were assigned to the tocilizumab and control groups, respectively. The mortality at day 28 was 24.4% and 29.9% in patients in the tocilizumab and control groups, respectively, meaning there was no significant difference observed between these two groups (OR, 0.92; 95% CI, 0.66-1.28; I2 = 62). This finding did not change in the subgroup analysis according to the initial use of MV or steroid while enrollment. The patients receiving tocilizumab had a lower rate of mechanical ventilation (MV) and intensive care unit (ICU) admission at day 28 compared with the control group (MV use: OR, 0.75; 95% CI, 0.62-0.90; I2 = 11; ICU admission: OR, 0.51; 95% CI, 0.28-0.92; I2 = 30). There were no significant differences between these two treatment groups in terms of the risk of treatment-emergent adverse events (AEs) (OR, 1.03; 95% CI, 0.71-1.49; I2 = 43), serious AEs (OR, 0.86; 95% CI, 0.67-1.12; I2 = 0) or infection (OR, 0.87; 95% CI, 0.63-1.20; I2 = 0).ConclusionsTocilizumab does not provide a survival benefit for patients with COVID-19, but it may help reduce the risk of MV and ICU admission. In addition, tocilizumab is a safe agent to use for the treatment of COVID-19.
| S-EPMC7988468 | biostudies-literature
Project description:This systemic review and meta-analysis aimed to assess the efficacy of tocilizumab for the treatment of severe coronavirus disease 2019 (COVID-19). Candidate studies up to 24 May 2020 were identified from PubMed, Cochrane Library, Embase, medRxiv and bioRxiv. Treatment outcomes included mortality, risk of intensive care unit (ICU) admission and the requirement for mechanical ventilation (MV). Seven retrospective studies involving 592 adult patients with severe COVID-19, including 240 in the tocilizumab group and 352 in the control group, were enrolled. All-cause mortality of severe COVID-19 patients among the tocilizumab group was 16.3% (39/240), which was lower than that in the control group (24.1%; 85/352). However, the difference did not reach statistical significance [risk ratio (RR) = 0.62, 95% confidence interval (CI) 0.31-1.22; I2 = 68%]. Additionally, risk of ICU admission was similar between the tocilizumab and control groups (35.1% vs. 15.8%; RR = 1.51, 95% CI 0.33-6.78; I2 = 86%). The requirement for MV was similar between the tocilizumab and control groups (32.4% vs. 28.6%; RR = 0.82, 95% CI 0.14-4.94; I2 = 91%). However, these non-significant differences between the tocilizumab and control groups may have been the result of baseline characteristics of the tocilizumab group, which were more severe than those of the control group. Based on low-quality evidence, there is no conclusive evidence that tocilizumab would provide any additional benefit to patients with severe COVID-19. Therefore, further recommendation of tocilizumab for COVID-19 cases should be halted until high-quality evidence from randomised controlled trials is available.
| S-EPMC7377685 | biostudies-literature
Project description:BackgroundThe majority of patients with coronavirus disease 2019 (COVID-19) have good prognoses, but some develop a critical illness that can lead to death. Evidence shows severe acute respiratory syndrome is closely related to the induced cytokine storm. Interleukin-6 is a key player; its role in systemic inflammation is well known.AimTo evaluate the effect of tocilizumab (TCZ), an interleukin-6 receptor antagonist, on the outcomes for patients with COVID-19 pneumonia.MethodsPubMed, EMBASE, SCOPUS, Web of Science, MedRxiv, Science Direct, and the Cochrane Library were searched from inception to 9th June 2020 for observational or prospective studies reporting results of hospitalized adult patients with COVID-19 infection treated with TCZ. Effect sizes were reported as odds ratios (ORs) with 95% confidence intervals (CIs), and an OR less than 1 was associated with a better outcome in those treated with TCZ.ResultsOverall 13476 patients (33 studies; n = 3264 received TCZ) with COVID-19 pneumonia and various degree of severity were included. Outcome was improved with TCZ. In the primary analysis (n = 19 studies reporting data), mortality was reduced in patients treated with TCZ (OR = 0.64, 95%CI: 0.47-0.87; P < 0.01). In 9 studies where risk of death with TCZ use was controlled for other variables mortality was reduced by 57% (OR = 0.43, 95%CI: 0.27-0.7; P < 0.01). Intensive care need (mechanical ventilation) was also reduced (OR = 0.36, 95%CI: 0.14-0.89; P = 0.02).ConclusionIn COVID-19-infected patients treated with TCZ, outcome may be improved compared to those not treated with TCZ.
| S-EPMC8127418 | biostudies-literature
Project description:BackgroundCoronavirus disease 2019 (COVID-19) has killed over 2.5 million people worldwide, but effective care and therapy have yet to be discovered. We conducted this analysis to better understand tocilizumab treatment for COVID-19 patients.Main textWe searched major databases for manuscripts reporting the effects of tocilizumab on COVID-19 patients. A total of 25 publications were analyzed with Revman 5.3 and R for the meta-analysis. Significant better clinical outcomes were found in the tocilizumab treatment group when compared to the standard care group [odds ratio (OR) = 0.70, 95% confidential interval (C): 0.54-0.90, P = 0.007]. Tocilizumab treatment showed a stronger correlation with good prognosis among COVID-19 patients that needed mechanical ventilation (OR = 0.59, 95% CI, 0.37-0.93, P = 0.02). Among stratified analyses, reduction of overall mortality correlates with tocilizumab treatment in patients less than 65 years old (OR = 0.68, 95% CI: 0.60-0.77, P < 0.00001), and with intensive care unit patients (OR = 0.62, 95% CI: 0.55-0.70, P < 0.00001). Pooled estimates of hazard ratio showed that tocilizumab treatment predicts better overall survival in COVID-19 patients (HR = 0.45, 95% CI: 0.24-0.84, P = 0.01), especially in severe cases (HR = 0.58, 95% CI 0.49-0.68, P < 0.00001).ConclusionsOur study shows that tocilizumab treatment is associated with a lower risk of mortality and mechanical ventilation requirement among COVID-19 patients. Tocilizumab may have substantial effectiveness in reducing mortality among COVID-19 patients, especially among critical cases. This systematic review provides an up-to-date evidence of potential therapeutic role of tocilizumab in COVID-19 management.
| S-EPMC8128625 | biostudies-literature
Project description:Introduction: Tocilizumab (TCZ) is an anti-interleukin-6 antibody that has been used for the treatment of severe coronavirus disease 2019 (COVID-19). However, concrete evidence of its benefit in reducing mortality in severe COVID-19 is lacking. Therefore, we performed a systematic review and meta-analysis of relevant studies that compared the efficacy of TCZ in severe COVID-19 vs. standard of care (SOC) alone. Methods: A literature search for studies that compared "tocilizumab" and "standard of care" in the treatment of COVID-19 was done using major online databases from December 2019 to June 14, 2020. Search words "Tocilizumab," "anti-interleukin-6 antibody," and "COVID-19" or "coronavirus 2019" in various combinations were used. Articles in the form of abstracts, letters without original data, case reports, and reviews were excluded. Data were gathered on an Excel sheet, and statistical analysis was performed using Review Manager 5.3. Results: Sixteen studies were eligible from 693 initial studies, including 3,641 patients (64% males). There were 13 retrospective studies and three prospective studies. There were 2,488 patients in the SOC group (61.7%) and 1,153 patients (68.7%) in the TCZ group. The death rate in the TCZ group, 22.4% (258/1,153), was lower than in the SOC group, 26.21% (652/2,488) [pooled odds ratio 0.57 (95% CI 0.36-0.92), p = 0.02]. There was a significant heterogeneity (inconsistency index = 80%) among the included studies. Conclusion: The addition of TCZ to the SOC might reduce mortality in severe COVID-19. More extensive randomized clinical trials are needed to validate these findings.
| S-EPMC7566918 | biostudies-literature
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.
| S-EPMC7652362 | biostudies-literature
Project description:We performed a meta-analysis to determine safety and efficacy of tocilizumab in persons with coronavirus disease-2019 (COVID-19). We searched PubMed, Web of Science and Medline using Boolean operators for studies with the terms coronavirus OR COVID-19 OR 2019-nCoV OR SARS-CoV-2 AND tocilizumab. Review Manager 5.4 was used to analyze data and the modified Newcastle-Ottawa and Jadad scales for quality assessment. We identified 32 studies in 11,487 subjects including three randomized trials and 29 cohort studies with a comparator cohort, including historical controls (N = 5), a matched cohort (N = 12), or concurrent controls (N = 12). Overall, tocilizumab decreased risk of death (Relative Risk [RR] = 0.74; 95% confidence interval [CI], 0.59, 0.93; P = 0.008; I2 = 80%) but not of surrogate endpoints including ICU admission (RR = 1.40 [0.64,3.06]; P = 0.4; I2 = 88%), invasive mechanical ventilation (RR = 0.83 [0.57,1.22]; P = 0.34; I2 = 65%) or secondary infections (RR = 1.30 [0.97,1.74]; P = 0.08; I2 = 65%) and increased interval of hospitalization of subjects discharged alive(mean difference [MD] = 2 days [<1, 4 days]; P = 0.006; I2 = 0). RRs of death in studies with historical controls (RR = 0.28 [0.16,0.49; P < 0.001]; I2 = 62%) or a matched cohort (RR = 0.68 [0.53, 0.87]; P = 0.002; I2 = 42%) were decreased. In contrast, RRs of death in studies with a concurrent control (RR = 1.10 [0.77, 1.56]; P = 0.60; I2 = 85%) or randomized (RR = 1.18 [0.57,2.44]; P = 0.66; I2 = 0) were not decreased. A reduced risk of death was not confirmed in our analyses which questions safety and efficacy of tocilizumab in persons with COVID-19.
| S-EPMC8127467 | biostudies-literature
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.
| S-EPMC7644182 | biostudies-literature
Project description: Not available
| S-EPMC8604568 | biostudies-literature