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Efficacy and safety of tocilizumab in COVID-19 patients: a living systematic review and meta-analysis, first update.
Clin Microbiol Infect. 2021 Aug; 27(8):1076-1082.CM

Abstract

OBJECTIVES

Cytokine 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 update the data in a living systematic review of the literature concerning the efficacy and toxicity of the IL-6 receptor antagonist tocilizumab in COVID-19 patients.

METHODS

Data 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 from 8th October 2020 till 24th February 2021. Eligible studies were randomized controlled trials (RCTs) and observational studies at low or moderate risk of bias. The participants were hospitalized COVID-19 patients, and intervention was tocilizumab versus placebo or standard of care. We pooled crude risk ratios (RRs) of RCTs with a random effects model and evaluated inconsistency between studies with I2. We assessed the certainty of evidence using the GRADE approach.

RESULTS

Of 1600 citations, eight RCTs and 28 cohorts were eligible. The eight RCTs had low risk of bias, and with 6311 patients they examined the effect of tocilizumab on short-term mortality; pooled RR was 0.91 (95%CI 0.78-1.07, I2 25%). Only the REMAP-CAP and RECOVERY trials, with the majority of their patients on concomitant corticosteroids, showed lower 30-day mortality with tocilizumab use: RR 0.74 (95%CI 0.59-0.93) and 0.89 (95%CI 0.81-0.97), respectively. Seven RCTs, with 5391 patients, examined the effect of tocilizumab on risk of mechanical ventilation; pooled RR was 0.84 (95%CI 0.76-0.93), I2 0%, with a corresponding number needed to treat of 20 (95%CI 14.3-33.3). Eight RCTs, with 5340 patients, examined the effect of tocilizumab on a composite of poor outcome; pooled RR was 0.82 (95%CI 0.76-0.90, I2 3%). Data from the RCTs showed a lower risk of infections and no higher risk of serious adverse events with tocilizumab: pooled RR 0.67 (95%CI 0.45-0.99, eight RCTs) and 0.85 (95%CI 0.63-1.16, seven RCTs), respectively. Among 28 cohorts with 15 484 patients, the pooled adjusted RR for mortality was 0.53 (95%CI 0.43-0.67, I2 76%).

CONCLUSIONS

Cumulative high-certainty evidence shows that tocilizumab reduces the risk of mechanical ventilation in hospitalized patients with severe COVID-19. Moderate-certainty evidence shows that tocilizumab reduces the risk of poor outcome and the risk of secondary infections in hospitalized COVID-19 patients. This review will continuously evaluate the role of tocilizumab in COVID-19 treatment.

Links

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Authors+Show Affiliations

Tleyjeh IM
Infectious Diseases Section, Department of Medical Specialties King Fahad Medical City, Riyadh, Saudi Arabia; College of Medicine, Alfaisal University, Riyadh, Saudi Arabia; Division of Infectious Diseases, Mayo Clinic College of Medicine and Science, Rochester, MN, USA; Division of Epidemiology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA. Electronic address: Tleyjeh.Imad@mayo.edu.
Kashour Z
Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
Riaz M
Department of Public Health, College of Health Sciences, QU Health, Qatar University, Doha, Qatar.
Hassett L
Mayo Clinic Libraries, Mayo Clinic, Rochester, MN, USA.
Veiga VC
BP-A Beneficência Portuguesa de São Paulo, Rua Maestro Cardim, São Paulo, Brazil; Brazilian Research in Intensive Care Network-BRICNet, São Paulo, SP, Brazil.
Kashour T
Department of Cardiac Sciences, King Fahad Cardiac Center, King Saud University Medical City, Riyadh, Saudi Arabia.

MeSH

Antibodies, Monoclonal, HumanizedCOVID-19HumansImmunosuppressive AgentsInterleukin-6Odds RatioPlacebosRespiration, ArtificialSARS-CoV-2Standard of CareTreatment OutcomeCOVID-19 Drug Treatment

Pub Type(s)

Journal Article
Meta-Analysis
Systematic Review

Language

eng

PubMed ID

33915284

Citation

Tleyjeh, Imad M., et al. "Efficacy and Safety of Tocilizumab in COVID-19 Patients: a Living Systematic Review and Meta-analysis, First Update." Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases, vol. 27, no. 8, 2021, pp. 1076-1082.
Tleyjeh IM, Kashour Z, Riaz M, et al. Efficacy and safety of tocilizumab in COVID-19 patients: a living systematic review and meta-analysis, first update. Clin Microbiol Infect. 2021;27(8):1076-1082.
Tleyjeh, I. M., Kashour, Z., Riaz, M., Hassett, L., Veiga, V. C., & Kashour, T. (2021). Efficacy and safety of tocilizumab in COVID-19 patients: a living systematic review and meta-analysis, first update. Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases, 27(8), 1076-1082. https://doi.org/10.1016/j.cmi.2021.04.019
Tleyjeh IM, et al. Efficacy and Safety of Tocilizumab in COVID-19 Patients: a Living Systematic Review and Meta-analysis, First Update. Clin Microbiol Infect. 2021;27(8):1076-1082. PubMed PMID: 33915284.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Efficacy and safety of tocilizumab in COVID-19 patients: a living systematic review and meta-analysis, first update. AU - Tleyjeh,Imad M, AU - Kashour,Zakariya, AU - Riaz,Muhammad, AU - Hassett,Leslie, AU - Veiga,Viviane C, AU - Kashour,Tarek, Y1 - 2021/04/27/ PY - 2021/2/1/received PY - 2021/4/15/revised PY - 2021/4/17/accepted PY - 2021/4/30/pubmed PY - 2021/8/17/medline PY - 2021/4/29/entrez KW - COVID KW - Meta-analysis KW - Outcome KW - Systematic review KW - Tocilizumab SP - 1076 EP - 1082 JF - Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases JO - Clin Microbiol Infect VL - 27 IS - 8 N2 - OBJECTIVES: Cytokine 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 update the data in a living systematic review of the literature concerning the efficacy and toxicity of the IL-6 receptor antagonist tocilizumab in COVID-19 patients. METHODS: Data 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 from 8th October 2020 till 24th February 2021. Eligible studies were randomized controlled trials (RCTs) and observational studies at low or moderate risk of bias. The participants were hospitalized COVID-19 patients, and intervention was tocilizumab versus placebo or standard of care. We pooled crude risk ratios (RRs) of RCTs with a random effects model and evaluated inconsistency between studies with I2. We assessed the certainty of evidence using the GRADE approach. RESULTS: Of 1600 citations, eight RCTs and 28 cohorts were eligible. The eight RCTs had low risk of bias, and with 6311 patients they examined the effect of tocilizumab on short-term mortality; pooled RR was 0.91 (95%CI 0.78-1.07, I2 25%). Only the REMAP-CAP and RECOVERY trials, with the majority of their patients on concomitant corticosteroids, showed lower 30-day mortality with tocilizumab use: RR 0.74 (95%CI 0.59-0.93) and 0.89 (95%CI 0.81-0.97), respectively. Seven RCTs, with 5391 patients, examined the effect of tocilizumab on risk of mechanical ventilation; pooled RR was 0.84 (95%CI 0.76-0.93), I2 0%, with a corresponding number needed to treat of 20 (95%CI 14.3-33.3). Eight RCTs, with 5340 patients, examined the effect of tocilizumab on a composite of poor outcome; pooled RR was 0.82 (95%CI 0.76-0.90, I2 3%). Data from the RCTs showed a lower risk of infections and no higher risk of serious adverse events with tocilizumab: pooled RR 0.67 (95%CI 0.45-0.99, eight RCTs) and 0.85 (95%CI 0.63-1.16, seven RCTs), respectively. Among 28 cohorts with 15 484 patients, the pooled adjusted RR for mortality was 0.53 (95%CI 0.43-0.67, I2 76%). CONCLUSIONS: Cumulative high-certainty evidence shows that tocilizumab reduces the risk of mechanical ventilation in hospitalized patients with severe COVID-19. Moderate-certainty evidence shows that tocilizumab reduces the risk of poor outcome and the risk of secondary infections in hospitalized COVID-19 patients. This review will continuously evaluate the role of tocilizumab in COVID-19 treatment. SN - 1469-0691 UR - https://www.unboundmedicine.com/medline/citation/33915284/Efficacy_and_safety_of_tocilizumab_in_COVID_19_patients:_a_living_systematic_review_and_meta_analysis_first_update_ DB - PRIME DP - Unbound Medicine ER -