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Tocilizumab in the treatment of COVID-19-a meta-analysis.
QJM. 2021 Nov 05; 114(8):577-586.QJM

Abstract

BACKGROUND

Interleukin-6 inhibitors showed promising results in observational trials of patients with coronavirus disease 2019 (COVID-19).

AIM

To evaluate whether interleukin-6 inhibitor tocilizumab (TCZ) reduces mortality among hospitalized COVID-19 patients.

DESIGN

A systematic review and meta-analysis.

METHODS

Systematic review and meta-analysis of randomized controlled trials (RCTs) comparing TCZ vs. placebo/control, for treatment of adults with COVID-19. Primary outcome was 28-30 days all-cause mortality. Search was conducted up to 1 April 2021. Two independent reviewers screened citations, extracted data and assessed risk of bias. Relative risk (RR) with 95% confidence intervals (CI) were pooled. We performed subgroup analysis for patients with critical illness and sensitivity analyses.

RESULTS

Eight RCTs were included, assessing 6481 patients with mostly severe non-critical COVID-19 infection. TCZ was associated with a reduction in all-cause 28-30-day mortality compared to placebo/control (RR = 0.89, 95% CI 0.82-0.96). Among the subgroup of critically ill patients no reduced mortality was demonstrated (RR = 0.94, 95% CI 0.74-1.19). No mortality benefit with TCZ was demonstrated in trials that used steroids for >80% of patients. TCZ was associated with significantly reduced risk for mechanical ventilation (MV); for combined endpoint of death or MV and for intensive care unit (ICU) admission. No significant difference in adverse events was demonstrated. Risk of serious superinfection was significantly lower with TCZ (RR = 0.57, 95% CI 0.35-0.93).

CONCLUSION

The treatment with TCZ reduces 28-30 days all-cause mortality, ICU admission, superinfections, MV and the combined endpoint of death or MV. Among critically ill patients, and when steroids were used for most patients, no mortality benefit was demonstrated. Additional research should further define sub-groups that would benefit most and preferred timing of administration of TCZ in severe COVID-19.

Authors+Show Affiliations

Department of Medicine A, Rabin Medical Center, Beilinson Hospital, 39 Jabotinsky Road, Petah-Tikva 49100, Israel. Unit of Infectious Diseases, Rabin Medical Center, Beilinson Hospital, 39 Jabotinsky Road, Petah-Tikva 49100, Israel. Sackler Faculty of Medicine, Tel-Aviv University, 39 Klatchkin st., Tel-Aviv 6997801, Israel.Sackler Faculty of Medicine, Tel-Aviv University, 39 Klatchkin st., Tel-Aviv 6997801, Israel. Research Authority, Rabin Medical Center, Beilinson Hospital, 39 Jabotinsky Road, Petah-Tikva 49100, Israel.Sackler Faculty of Medicine, Tel-Aviv University, 39 Klatchkin st., Tel-Aviv 6997801, Israel.Unit of Infectious Diseases, Rabin Medical Center, Beilinson Hospital, 39 Jabotinsky Road, Petah-Tikva 49100, Israel. Sackler Faculty of Medicine, Tel-Aviv University, 39 Klatchkin st., Tel-Aviv 6997801, Israel.Department of Medicine A, Rabin Medical Center, Beilinson Hospital, 39 Jabotinsky Road, Petah-Tikva 49100, Israel.Unit of Infectious Diseases, Rambam Health Care Campus and Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Efron 1 st, Haifa 3200003, Israel.Department of Medicine A, Rabin Medical Center, Beilinson Hospital, 39 Jabotinsky Road, Petah-Tikva 49100, Israel. Sackler Faculty of Medicine, Tel-Aviv University, 39 Klatchkin st., Tel-Aviv 6997801, Israel.Unit of Infectious Diseases, Rabin Medical Center, Beilinson Hospital, 39 Jabotinsky Road, Petah-Tikva 49100, Israel. Sackler Faculty of Medicine, Tel-Aviv University, 39 Klatchkin st., Tel-Aviv 6997801, Israel.

Pub Type(s)

Journal Article
Meta-Analysis
Systematic Review

Language

eng

PubMed ID

34010403

Citation

Avni, T, et al. "Tocilizumab in the Treatment of COVID-19-a Meta-analysis." QJM : Monthly Journal of the Association of Physicians, vol. 114, no. 8, 2021, pp. 577-586.
Avni T, Leibovici L, Cohen I, et al. Tocilizumab in the treatment of COVID-19-a meta-analysis. QJM. 2021;114(8):577-586.
Avni, T., Leibovici, L., Cohen, I., Atamna, A., Guz, D., Paul, M., Gafter-Gvili, A., & Yahav, D. (2021). Tocilizumab in the treatment of COVID-19-a meta-analysis. QJM : Monthly Journal of the Association of Physicians, 114(8), 577-586. https://doi.org/10.1093/qjmed/hcab142
Avni T, et al. Tocilizumab in the Treatment of COVID-19-a Meta-analysis. QJM. 2021 Nov 5;114(8):577-586. PubMed PMID: 34010403.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tocilizumab in the treatment of COVID-19-a meta-analysis. AU - Avni,T, AU - Leibovici,L, AU - Cohen,I, AU - Atamna,A, AU - Guz,D, AU - Paul,M, AU - Gafter-Gvili,A, AU - Yahav,D, PY - 2021/05/03/received PY - 2021/05/05/revised PY - 2021/5/20/pubmed PY - 2021/11/10/medline PY - 2021/5/19/entrez SP - 577 EP - 586 JF - QJM : monthly journal of the Association of Physicians JO - QJM VL - 114 IS - 8 N2 - BACKGROUND: Interleukin-6 inhibitors showed promising results in observational trials of patients with coronavirus disease 2019 (COVID-19). AIM: To evaluate whether interleukin-6 inhibitor tocilizumab (TCZ) reduces mortality among hospitalized COVID-19 patients. DESIGN: A systematic review and meta-analysis. METHODS: Systematic review and meta-analysis of randomized controlled trials (RCTs) comparing TCZ vs. placebo/control, for treatment of adults with COVID-19. Primary outcome was 28-30 days all-cause mortality. Search was conducted up to 1 April 2021. Two independent reviewers screened citations, extracted data and assessed risk of bias. Relative risk (RR) with 95% confidence intervals (CI) were pooled. We performed subgroup analysis for patients with critical illness and sensitivity analyses. RESULTS: Eight RCTs were included, assessing 6481 patients with mostly severe non-critical COVID-19 infection. TCZ was associated with a reduction in all-cause 28-30-day mortality compared to placebo/control (RR = 0.89, 95% CI 0.82-0.96). Among the subgroup of critically ill patients no reduced mortality was demonstrated (RR = 0.94, 95% CI 0.74-1.19). No mortality benefit with TCZ was demonstrated in trials that used steroids for >80% of patients. TCZ was associated with significantly reduced risk for mechanical ventilation (MV); for combined endpoint of death or MV and for intensive care unit (ICU) admission. No significant difference in adverse events was demonstrated. Risk of serious superinfection was significantly lower with TCZ (RR = 0.57, 95% CI 0.35-0.93). CONCLUSION: The treatment with TCZ reduces 28-30 days all-cause mortality, ICU admission, superinfections, MV and the combined endpoint of death or MV. Among critically ill patients, and when steroids were used for most patients, no mortality benefit was demonstrated. Additional research should further define sub-groups that would benefit most and preferred timing of administration of TCZ in severe COVID-19. SN - 1460-2393 UR - https://www.unboundmedicine.com/medline/citation/34010403/Tocilizumab_in_the_treatment_of_COVID_19_a_meta_analysis_ L2 - https://academic.oup.com/qjmed/article-lookup/doi/10.1093/qjmed/hcab142 DB - PRIME DP - Unbound Medicine ER -