Efficacy and harms of tocilizumab for the treatment of COVID-19 patients: A systematic review and meta-analysis

Abstract

Introduction We systematically assessed benefits and harms of tocilizumab (TCZ), which is an antibody blocking IL-6 receptors, in hospitalized COVID-19 patients. Methods Five electronic databases and two preprint webpages were searched until March 4, 2021. Randomized controlled trials (RCTs) and inverse probability treatment weighting (IPTW) cohorts assessing TCZ effects in hospitalized, COVID-19 adult patients were included. Primary outcomes were all-cause mortality, clinical worsening, clinical improvement, need for mechanical ventilation, and adverse events (AE). Inverse variance random-effects meta-analyses were performed with quality of evidence (QoE) evaluated using GRADE methodology. Results Nine RCTs (n = 7,021) and nine IPTW cohorts (n = 7,796) were included. TCZ significantly reduced all-cause mortality in RCTs (RR 0.89, 95%CI 0.81–0.98, p = 0.03; moderate QoE) and non-significantly in cohorts (RR 0.67, 95%CI 0.44–1.02, p = 0.08; very low QoE) vs. control (standard of care [SOC] or placebo). TCZ significantly reduced the need for mechanical ventilation (RR 0.80, 95%CI 0.71–0.90, p = 0.001; moderate QoE) and length of stay (MD -1.92 days, 95%CI -3.46 to -0.38, p = 0.01; low QoE) vs. control in RCTs. There was no significant difference in clinical improvement or worsening between treatments. AEs, severe AEs, bleeding and thrombotic events were similar between arms in RCTs, but there was higher neutropenia risk with TCZ (very low QoE). Subgroup analyses by disease severity or risk of bias (RoB) were consistent with main analyses. Quality of evidence was moderate to very low in both RCTs and cohorts. Conclusions In comparison to SOC or placebo, TCZ reduced all-cause mortality in all studies and reduced mechanical ventilation and length of stay in RCTs in hospitalized COVID-19 patients. Other clinical outcomes were not significantly impacted. TCZ did not have effect on AEs, except a significant increased neutropenia risk in RCTs. TCZ has a potential role in the treatment of hospitalized COVID-19 patients.

Factors predicting poor outcomes of patients treated with tocilizumab for COVID‑19‑associated pneumonia: A retrospective study

“…The mortality rate found in the present study was relatively higher compared to the rates demonstrated in randomized controlled trials of tocilizumab and in meta-analyses mentioning a pooled mortality prevalence of 20-30% (17)(18)(19)(20)(21). One of the main findings of the present study was that among all patients treated with tocilizumab for COVID-19-associated pneumonia, age was the only independent factor predicting 90-day mortality.…”

Artificial intelligence assessment of the potential of tocilizumab along with corticosteroids therapy for the management of COVID-19 evoked acute respiratory distress syndrome

“…As commented, the study by Ullah et al [ 67 ], highlights the role of tocilizumab in improving performance on an institutional treatment including dexamethasone over coagulopathy control, supporting our model results. Furthermore, the evidence regarding the use of biologics targeting IL-6R –including tocilizumab–and IL-6 downstream JAK proteins since we started this study has increased [ 40 , 41 , 86 – 90 ], to the point that its use is recommended in the NIH guidelines for treatment of hospitalized patients requiring oxygen or assisted ventilation or oxygenation, in combination to dexamethasone [ 91 ] The methodology employed for the modelling, considering the whole human protein network and a wide range of drug-pathology relationships for the training ( S4 Table ), allow the TPMS-based models to infer biological and functional information on not-so-well documented therapeutic areas by connecting a wider biological knowledge spectrum, as shown in previous studies [ 47 , 55 , 83 , 84 ].Therefore, while the models and conclusions could be updated over time as new information is generated, potentially improving accuracy of the results and allowing exploring unanswered questions in COVID-19 evoked ARDS, our approach has provided results that are in agreement with current molecular pathophysiological and clinical knowledge, providing protein candidates as response biomarkers and supporting the role of the approach in exploring mechanistic insights on the effects of current available therapies.…”

Identification of Clinical Response Predictors of Tocilizumab Treatment in Patients with Severe COVID-19 Based on Single-Center Experience

“…In RCTs with IL-6 inhibitors, serious adverse events (SAE) were not occurring more frequently in TCZ groups than in comparators (usually including DEX). Most concerns were linked to secondary infections; however, such a risk was not reported in several RCTs and meta-analyses [ 29 , 30 , 32 , 97 , 98 ]. Moreover, some found lower serious infection rates or even fewer severe advent events in patients receiving TCZ added to standard of care (SoC) vs. SoC alone [ 98 , 99 ].…”