Abstract
To explore and summarize the association between treatment with tocilizumab and clinical outcomes in COVID-19 patients. We performed a systematic review and meta-analysis (10 RCTs including 3378 patients in the tocilizumab group and 3142 patients in the control group). We systematically searched PubMed and MedRxiv for all RCTs as of June 1, 2021, to assess the benefits and harms of tocilizumab to treat patients with COVID-19. All analyses were carried out using RevMan version 5.4.1. There were nine RCTs published in peer-reviewed journals and one RCTs published as a preprint. The summary RR for all-cause mortality with tocilizumab was 0.89 (95% CI= 0.82-0.96, P= 0.003). There was no significant between-trial heterogeneity (I2= 28%, P= 0.19). However, all peer-reviewed RCTs showed no significant associations between treatment with tocilizumab and reductions in all-cause mortality. We notably found that tocilizumab significantly reduced the rate of intubation or death in patients with COVID-19 with 3 RCTs. Across the 8 RCTs, the summary RR for discharge with tocilizumab was 1.10 (95% CI= 1.03-1.16, P< 0.00001). There was no significant association of tocilizumab with harm on other patient-relevant clinical outcomes, including increasing secondary infection risk, patients of adverse events, or patients of serious adverse events. Tocilizumab significantly increased the rate of hospital discharges in COVID-19 patients. Still, it did not decrease all-cause mortality or increase the risk of secondary infections, patients of adverse events, or patients for serious adverse events. Evidence that tocilizumab affects clinical outcomes in patients with COVID-19 requires further proof.
Highlights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel human pathogen, is one of the most considerable global challenges facing public health and humanity [1,2,3]
From 9 randomized clinical trial (RCT) published in peer-reviewed journals, there were 2404 patients (1048 to placebo together with the standard of care or only standard of care and 1356 randomized to tocilizumab) in our meta-analysis
We notably found that tocilizumab significantly reduced the rate of intubation or death in patients with COVID-19 with 3 RCTs (RR= 0.85, 95% confidence intervals (CI)= 0.78-0.92, P= 0.0002) (Figure 1A, 1D, and Supplementary Figure 1)
Summary
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel human pathogen, is one of the most considerable global challenges facing public health and humanity [1,2,3]. COVID-19 is associated with dysregulated immune responses and hyper inflammation, including releasing of proinflammatory cytokines and chemokines. It can cause or worsen acute respiratory distress syndrome and multiple organ failure [13,14,15]. The randomized evaluation of the COVID-19 therapy platform (RECOVERY) trial is by far the largest randomized clinical trial (RCT) on COVID-19 treatments [21]. It has provided essential evidence for several promising therapies, including hydroxychloroquine, dexamethasone, lopinavirritonavir, convalescent plasma, and azithromycin
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