Tocilizumab for Treatment of Mechanically Ventilated Patients With COVID-19.
COVID-19
SARS-CoV-2
interleukin-6
tocilizumab
Journal
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213
Informations de publication
Date de publication:
15 07 2021
15 07 2021
Historique:
received:
05
06
2020
accepted:
09
07
2020
pubmed:
12
7
2020
medline:
21
7
2021
entrez:
12
7
2020
Statut:
ppublish
Résumé
Severe coronavirus disease 2019 (COVID-19) can manifest in rapid decompensation and respiratory failure with elevated inflammatory markers, consistent with cytokine release syndrome for which IL-6 blockade is an approved treatment. We assessed effectiveness and safety of IL-6 blockade with tocilizumab in a single-center cohort of patients with COVID-19 requiring mechanical ventilation. The primary endpoint was survival probability postintubation; secondary analyses included an ordinal illness severity scale integrating superinfections. Outcomes in patients who received tocilizumab compared with tocilizumab-untreated controls were evaluated using multivariable Cox regression with propensity score inverse probability of treatment weighting (IPTW). 154 patients were included, of whom 78 received tocilizumab and 76 did not. Median follow-up was 47 days (range, 28-67). Baseline characteristics were similar between groups, although tocilizumab-treated patients were younger (mean: 55 vs 60 years), less likely to have chronic pulmonary disease (10% vs 28%), and had lower D-dimer values at time of intubation (median: 2.4 vs 6.5 mg/dL). In IPTW-adjusted models, tocilizumab was associated with a 45% reduction in hazard of death (HR, .55; 95% CI, .33-.90) and improved status on the ordinal outcome scale [OR per 1-level increase, .58; .36-.94). Although tocilizumab was associated with an increased proportion of patients with superinfections (54% vs 26%; P < .001), there was no difference in 28-day case fatality rate among tocilizumab-treated patients with versus without superinfection (22% vs 15%; P = .42). Staphylococcus aureus accounted for ~50% of bacterial pneumonia. In this cohort of mechanically ventilated COVID-19 patients, tocilizumab was associated with lower mortality despite higher superinfection occurrence.
Sections du résumé
BACKGROUND
Severe coronavirus disease 2019 (COVID-19) can manifest in rapid decompensation and respiratory failure with elevated inflammatory markers, consistent with cytokine release syndrome for which IL-6 blockade is an approved treatment.
METHODS
We assessed effectiveness and safety of IL-6 blockade with tocilizumab in a single-center cohort of patients with COVID-19 requiring mechanical ventilation. The primary endpoint was survival probability postintubation; secondary analyses included an ordinal illness severity scale integrating superinfections. Outcomes in patients who received tocilizumab compared with tocilizumab-untreated controls were evaluated using multivariable Cox regression with propensity score inverse probability of treatment weighting (IPTW).
RESULTS
154 patients were included, of whom 78 received tocilizumab and 76 did not. Median follow-up was 47 days (range, 28-67). Baseline characteristics were similar between groups, although tocilizumab-treated patients were younger (mean: 55 vs 60 years), less likely to have chronic pulmonary disease (10% vs 28%), and had lower D-dimer values at time of intubation (median: 2.4 vs 6.5 mg/dL). In IPTW-adjusted models, tocilizumab was associated with a 45% reduction in hazard of death (HR, .55; 95% CI, .33-.90) and improved status on the ordinal outcome scale [OR per 1-level increase, .58; .36-.94). Although tocilizumab was associated with an increased proportion of patients with superinfections (54% vs 26%; P < .001), there was no difference in 28-day case fatality rate among tocilizumab-treated patients with versus without superinfection (22% vs 15%; P = .42). Staphylococcus aureus accounted for ~50% of bacterial pneumonia.
CONCLUSIONS
In this cohort of mechanically ventilated COVID-19 patients, tocilizumab was associated with lower mortality despite higher superinfection occurrence.
Identifiants
pubmed: 32651997
pii: 5870306
doi: 10.1093/cid/ciaa954
pmc: PMC7454462
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
tocilizumab
I031V2H011
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e445-e454Subventions
Organisme : NIH HHS
ID : UL1TR002240
Pays : United States
Organisme : American Society for Transplantation and Cellular Therapy New Investigator Award
Organisme : NHLBI NIH HHS
ID : K12 HL133304
Pays : United States
Organisme : CDC HHS
ID : U01IP000974
Pays : United States
Organisme : ACL HHS
ID : U01IP000974
Pays : United States
Commentaires et corrections
Type : UpdateOf
Type : CommentIn
Informations de copyright
© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.
Références
Am J Epidemiol. 2008 Feb 15;167(4):492-9
pubmed: 18056625
Chest. 2007 Aug;132(2):410-7
pubmed: 17573487
J Med Virol. 2020 Jul;92(7):814-818
pubmed: 32253759
Clin Exp Rheumatol. 2020 May-Jun;38(3):529-532
pubmed: 32359035
Lancet Infect Dis. 2014 Jan;14(1):8-9
pubmed: 24355025
BMJ. 2020 May 22;369:m1966
pubmed: 32444366
Autoimmun Rev. 2020 Jun;19(6):102537
pubmed: 32251717
Front Microbiol. 2019 May 10;10:1057
pubmed: 31134045
JAMA Intern Med. 2020 Jul 1;180(7):934-943
pubmed: 32167524
Lancet. 2020 Mar 28;395(10229):1033-1034
pubmed: 32192578
Chest. 2020 Jul;158(1):e15-e19
pubmed: 32343968
Med Mal Infect. 2020 Aug;50(5):397-400
pubmed: 32387320
Sci Rep. 2016 Aug 26;6:32188
pubmed: 27561337
Epidemiology. 2007 Nov;18(6):805-35
pubmed: 18049195
N Engl J Med. 2020 Apr 30;382(18):1708-1720
pubmed: 32109013
Lancet Rheumatol. 2020 Jul;2(7):e428-e436
pubmed: 32835246
Autoimmun Rev. 2020 Jul;19(7):102564
pubmed: 32376396
Science. 2020 May 1;368(6490):473-474
pubmed: 32303591
Stat Methods Med Res. 2007 Jun;16(3):219-42
pubmed: 17621469
Int J Radiat Oncol Biol Phys. 2012 Dec 1;84(5):1078-85
pubmed: 22867894
Lancet Infect Dis. 2020 Jul;20(7):770-772
pubmed: 32502433
Intensive Care Med. 2020 May;46(5):846-848
pubmed: 32125452
Sci Rep. 2017 Mar 06;7:43829
pubmed: 28262742
Blood. 2013 Jun 27;121(26):5154-7
pubmed: 23678006
Eur J Intern Med. 2020 Jun;76:31-35
pubmed: 32405160
Hypertension. 2019 Apr;73(4):829-838
pubmed: 30739537
Stat Med. 2015 Dec 10;34(28):3661-79
pubmed: 26238958
Proc Natl Acad Sci U S A. 2020 May 19;117(20):10970-10975
pubmed: 32350134