Tocilizumab for Treatment of Mechanically Ventilated Patients With COVID-19.


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
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-e454

Subventions

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.

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Auteurs

Emily C Somers (EC)

Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Department of Environmental Health Sciences, University of Michigan, Ann Arbor, Michigan, USA.
Department of Obstetrics & Gynecology, University of Michigan, Ann Arbor, Michigan, USA.

Gregory A Eschenauer (GA)

Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, Michigan, USA.

Jonathan P Troost (JP)

Michigan Institute for Clinical & Health Research, University of Michigan, Ann Arbor, Michigan, USA.

Jonathan L Golob (JL)

Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.

Tejal N Gandhi (TN)

Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.

Lu Wang (L)

Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.

Nina Zhou (N)

Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.

Lindsay A Petty (LA)

Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.

Ji Hoon Baang (JH)

Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.

Nicholas O Dillman (NO)

Department of Pharmacy, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA.

David Frame (D)

Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, Michigan, USA.

Kevin S Gregg (KS)

Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.

Dan R Kaul (DR)

Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.

Jerod Nagel (J)

Department of Pharmacy, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA.

Twisha S Patel (TS)

Department of Pharmacy, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA.

Shiwei Zhou (S)

Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.

Adam S Lauring (AS)

Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.

David A Hanauer (DA)

Department of Learning Health Sciences, University of Michigan, Ann Arbor, Michigan, USA.

Emily Martin (E)

Department of Epidemiology, University of Michigan, Ann Arbor, Michigan, USA.

Pratima Sharma (P)

Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.

Christopher M Fung (CM)

Department of Emergency Medicine, University of Michigan, Ann Arbor, Michigan, USA.

Jason M Pogue (JM)

Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, Michigan, USA.

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