The Use of Tocilizumab in Patients with COVID-19: A Systematic Review, Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Studies.

COVID-19 COVID-19 pneumonia SARS-CoV-2 meta-analysis tocilizumab trial sequential analysis

Journal

Journal of clinical medicine
ISSN: 2077-0383
Titre abrégé: J Clin Med
Pays: Switzerland
ID NLM: 101606588

Informations de publication

Date de publication:
25 Oct 2021
Historique:
received: 26 08 2021
revised: 21 10 2021
accepted: 23 10 2021
entrez: 13 11 2021
pubmed: 14 11 2021
medline: 14 11 2021
Statut: epublish

Résumé

Among the several therapeutic options assessed for the treatment of coronavirus disease 2019 (COVID-19), tocilizumab (TCZ), an antagonist of the interleukine-6 receptor, has emerged as a promising therapeutic choice, especially for the severe form of the disease. Proper synthesis of the available randomized clinical trials (RCTs) is needed to inform clinical practice. A systematic review with a meta-analysis of RCTs investigating the efficacy of TCZ in COVID-19 patients was conducted. PubMed, EMBASE, and the Cochrane COVID-19 Study Register were searched up until 30 April 2021. The database search yielded 2885 records; 11 studies were considered eligible for full-text review, and nine met the inclusion criteria. Overall, 3358 patients composed the TCZ arm, and 3131 the comparator group. The main outcome was all-cause mortality at 28-30 days. Subgroup analyses according to trials' and patients' features were performed. A trial sequential analysis (TSA) was also carried out to minimize type I and type II errors. According to the fixed-effect model approach, TCZ was associated with a better survival odds ratio (OR) (0.84; 95% confidence interval (CI): 0.75-0.94; I TCZ may represent an important weapon against severe COVID-19. Further studies are needed to consolidate this finding.

Sections du résumé

BACKGROUND BACKGROUND
Among the several therapeutic options assessed for the treatment of coronavirus disease 2019 (COVID-19), tocilizumab (TCZ), an antagonist of the interleukine-6 receptor, has emerged as a promising therapeutic choice, especially for the severe form of the disease. Proper synthesis of the available randomized clinical trials (RCTs) is needed to inform clinical practice.
METHODS METHODS
A systematic review with a meta-analysis of RCTs investigating the efficacy of TCZ in COVID-19 patients was conducted. PubMed, EMBASE, and the Cochrane COVID-19 Study Register were searched up until 30 April 2021.
RESULTS RESULTS
The database search yielded 2885 records; 11 studies were considered eligible for full-text review, and nine met the inclusion criteria. Overall, 3358 patients composed the TCZ arm, and 3131 the comparator group. The main outcome was all-cause mortality at 28-30 days. Subgroup analyses according to trials' and patients' features were performed. A trial sequential analysis (TSA) was also carried out to minimize type I and type II errors. According to the fixed-effect model approach, TCZ was associated with a better survival odds ratio (OR) (0.84; 95% confidence interval (CI): 0.75-0.94; I
CONCLUSIONS CONCLUSIONS
TCZ may represent an important weapon against severe COVID-19. Further studies are needed to consolidate this finding.

Identifiants

pubmed: 34768455
pii: jcm10214935
doi: 10.3390/jcm10214935
pmc: PMC8584705
pii:
doi:

Types de publication

Journal Article Review

Langues

eng

Références

N Engl J Med. 2021 Apr 22;384(16):1491-1502
pubmed: 33631065
Lancet Respir Med. 2021 Jun;9(6):655-664
pubmed: 33930329
N Engl J Med. 2020 Dec 3;383(23):2255-2273
pubmed: 33264547
Am J Epidemiol. 2021 Aug 1;190(8):1452-1456
pubmed: 33564823
Lancet Microbe. 2021 Jan;2(1):e13-e22
pubmed: 33521734
Cochrane Database Syst Rev. 2021 Aug 5;8:CD014962
pubmed: 34350582
Am J Pathol. 2021 Jan;191(1):4-17
pubmed: 32919977
BMJ. 2011 Oct 18;343:d5928
pubmed: 22008217
JAMA Intern Med. 2021 Jan 1;181(1):32-40
pubmed: 33080017
Eur J Epidemiol. 2020 Jan;35(1):49-60
pubmed: 31720912
Clin Microbiol Infect. 2021 Feb;27(2):215-227
pubmed: 33161150
Ir J Med Sci. 2021 Feb;190(1):11-12
pubmed: 32468413
Immunity. 2019 Apr 16;50(4):1007-1023
pubmed: 30995492
Open Forum Infect Dis. 2021 Jul 01;8(8):ofab317
pubmed: 34377723
Contemp Clin Trials. 2015 Nov;45(Pt A):139-45
pubmed: 26343745
J Immunother Cancer. 2020 Aug;8(2):
pubmed: 32784217
Intensive Care Med. 2021 Jun;47(6):641-652
pubmed: 34019122
Thorax. 2021 Sep;76(9):907-919
pubmed: 33579777
Clin Microbiol Infect. 2021 Jul;27(7):949-957
pubmed: 33813117
BMJ Open. 2016 Aug 12;6(8):e011890
pubmed: 27519923
J Infect. 2021 May;82(5):178-185
pubmed: 33745918
Lancet. 2021 May 01;397(10285):1637-1645
pubmed: 33933206
BMJ. 2021 Mar 29;372:n71
pubmed: 33782057
JAMA Intern Med. 2021 Jan 1;181(1):24-31
pubmed: 33080005
Cochrane Database Syst Rev. 2021 Mar 18;3:CD013881
pubmed: 33734435
Infect Dis Ther. 2021 Sep;10(3):1195-1213
pubmed: 34247325
Ann Intern Med. 2021 May;174(5):663-672
pubmed: 33560863
J Transl Med. 2020 Apr 14;18(1):165
pubmed: 32290847
J Clin Epidemiol. 2009 Aug;62(8):825-830.e10
pubmed: 19136233
Semin Immunol. 2014 Feb;26(1):88-96
pubmed: 24594001
Front Immunol. 2020 Jul 10;11:1708
pubmed: 32754163
JAMA. 2020 Oct 6;324(13):1330-1341
pubmed: 32876694
J Antimicrob Chemother. 2021 Jan 19;76(2):283-285
pubmed: 33099620
J Immunother Cancer. 2021 Apr;9(4):
pubmed: 33837054
Anesth Pain Med (Seoul). 2021 Apr;16(2):138-150
pubmed: 33940767
BMJ. 2021 Jan 20;372:n84
pubmed: 33472855
Lancet Respir Med. 2021 May;9(5):511-521
pubmed: 33676589
BMJ. 1997 Sep 13;315(7109):629-34
pubmed: 9310563
N Engl J Med. 2020 Dec 10;383(24):2333-2344
pubmed: 33085857
Lancet Respir Med. 2021 May;9(5):522-532
pubmed: 33676590
Immun Inflamm Dis. 2021 Mar;9(1):31-36
pubmed: 33244901
Anaesthesia. 2020 Jan;75(1):15-20
pubmed: 31106849
Lancet Respir Med. 2021 Jun;9(6):643-654
pubmed: 33872590
J Med Libr Assoc. 2017 Jan;105(1):84-87
pubmed: 28096751
Sci Prog. 2021 Jul-Sep;104(3):368504211030372
pubmed: 34236264
BMC Med Res Methodol. 2019 Oct 26;19(1):198
pubmed: 31655550
Am J Health Syst Pharm. 2008 Aug 1;65(15):1413-8
pubmed: 18653811
Mult Scler Relat Disord. 2020 Nov;46:102483
pubmed: 32942119
Lung. 2021 Jun;199(3):239-248
pubmed: 34050796
N Engl J Med. 2021 Apr 22;384(16):1503-1516
pubmed: 33631066
N Engl J Med. 2021 Jan 7;384(1):20-30
pubmed: 33332779
JAMA. 2021 Aug 10;326(6):499-518
pubmed: 34228774
BMJ. 2003 Sep 6;327(7414):557-60
pubmed: 12958120

Auteurs

Alberto Enrico Maraolo (AE)

First Division of Infectious Diseases, Cotugno Hospital, AORN dei Colli, 80131 Naples, Italy.

Anna Crispo (A)

Epidemiology and Biostatistics Unit, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, 80131 Naples, Italy.

Michela Piezzo (M)

Department of Public Health and Infectious Diseases, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy.

Piergiacomo Di Gennaro (P)

Epidemiology and Biostatistics Unit, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, 80131 Naples, Italy.

Maria Grazia Vitale (MG)

Department of Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto NazionaleTumori, IRCCS Fondazione G. Pascale, 80131 Naples, Italy.

Domenico Mallardo (D)

Department of Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto NazionaleTumori, IRCCS Fondazione G. Pascale, 80131 Naples, Italy.

Luigi Ametrano (L)

Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, 80131 Naples, Italy.

Egidio Celentano (E)

Epidemiology and Biostatistics Unit, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, 80131 Naples, Italy.

Arturo Cuomo (A)

Division of Anesthesia and Pain Medicine, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, 80131 Naples, Italy.

Paolo A Ascierto (PA)

Department of Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto NazionaleTumori, IRCCS Fondazione G. Pascale, 80131 Naples, Italy.

Marco Cascella (M)

Division of Anesthesia and Pain Medicine, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, 80131 Naples, Italy.

Classifications MeSH