Tocilizumab for the Treatment of COVID-19 Among Hospitalized Patients: A Matched Retrospective Cohort Analysis.
COVID-19
IL-6
SARS-CoV-2
retrospective
tocilizumab
Journal
Open forum infectious diseases
ISSN: 2328-8957
Titre abrégé: Open Forum Infect Dis
Pays: United States
ID NLM: 101637045
Informations de publication
Date de publication:
Jan 2021
Jan 2021
Historique:
received:
20
11
2020
accepted:
02
12
2020
entrez:
4
2
2021
pubmed:
5
2
2021
medline:
5
2
2021
Statut:
epublish
Résumé
There is currently no single treatment that mitigates all harms caused by severe acute respiratory syndrome coronavirus 2 infection. Tocilizumab, an interleukin-6 antagonist, may have a role as an adjunctive immune-modulating therapy. This was an observational retrospective study of hospitalized adult patients with confirmed coronavirus disease 2019 (COVID-19). The intervention group comprised patients who received tocilizumab; the comparator arm was drawn from patients who did not receive tocilizumab. The primary outcome was all-cause mortality censored at 28 days; secondary outcomes were all-cause mortality at discharge, time to clinical improvement, and rates of secondary infections. Marginal structural Cox models via inverse probability treatment weights were applied to estimate the effect of tocilizumab. A time-dependent propensity score-matching method was used to generate a 1:1 match for tocilizumab recipients; infectious diseases experts then manually reviewed these matched charts to identify secondary infections. This analysis included 90 tocilizumab recipients and 1669 controls. Under the marginal structural Cox model, tocilizumab was associated with a 62% reduced hazard of death (adjusted hazard ratio [aHR], 0.38; 95% CI, 0.21 to 0.70) and no change in time to clinical improvement (aHR, 1.13; 95% CI, 0.68 to 1.87). The 1:1 matched data set also showed a lower mortality rate (27.8% vs 34.4%) and reduced hazards of death (aHR, 0.47; 95% CI, 0.25 to 0.88). Elevated inflammatory markers were associated with reduced hazards of death among tocilizumab recipients compared with controls. Secondary infection rates were similar between the 2 groups. Tocilizumab may provide benefit in a subgroup of patients hospitalized with COVID-19 who have elevated biomarkers of hyperinflammation, without increasing the risk of secondary infection.
Sections du résumé
BACKGROUND
BACKGROUND
There is currently no single treatment that mitigates all harms caused by severe acute respiratory syndrome coronavirus 2 infection. Tocilizumab, an interleukin-6 antagonist, may have a role as an adjunctive immune-modulating therapy.
METHODS
METHODS
This was an observational retrospective study of hospitalized adult patients with confirmed coronavirus disease 2019 (COVID-19). The intervention group comprised patients who received tocilizumab; the comparator arm was drawn from patients who did not receive tocilizumab. The primary outcome was all-cause mortality censored at 28 days; secondary outcomes were all-cause mortality at discharge, time to clinical improvement, and rates of secondary infections. Marginal structural Cox models via inverse probability treatment weights were applied to estimate the effect of tocilizumab. A time-dependent propensity score-matching method was used to generate a 1:1 match for tocilizumab recipients; infectious diseases experts then manually reviewed these matched charts to identify secondary infections.
RESULTS
RESULTS
This analysis included 90 tocilizumab recipients and 1669 controls. Under the marginal structural Cox model, tocilizumab was associated with a 62% reduced hazard of death (adjusted hazard ratio [aHR], 0.38; 95% CI, 0.21 to 0.70) and no change in time to clinical improvement (aHR, 1.13; 95% CI, 0.68 to 1.87). The 1:1 matched data set also showed a lower mortality rate (27.8% vs 34.4%) and reduced hazards of death (aHR, 0.47; 95% CI, 0.25 to 0.88). Elevated inflammatory markers were associated with reduced hazards of death among tocilizumab recipients compared with controls. Secondary infection rates were similar between the 2 groups.
CONCLUSIONS
CONCLUSIONS
Tocilizumab may provide benefit in a subgroup of patients hospitalized with COVID-19 who have elevated biomarkers of hyperinflammation, without increasing the risk of secondary infection.
Identifiants
pubmed: 33537364
doi: 10.1093/ofid/ofaa598
pii: ofaa598
pmc: PMC7798657
doi:
Types de publication
Journal Article
Langues
eng
Pagination
ofaa598Subventions
Organisme : NIAID NIH HHS
ID : T32 AI007291
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM066691
Pays : United States
Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.
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