tetano
Editor, Senior Moderator
Open Forum Infect Dis
. 2020 Dec 28;8(1)
faa598.
doi: 10.1093/ofid/ofaa598. eCollection 2021 Jan.
Tocilizumab for the Treatment of COVID-19 Among Hospitalized Patients: A Matched Retrospective Cohort Analysis
Elisa H Ignatius[SUP] 1 2 [/SUP], Kunbo Wang[SUP] 2 3 [/SUP], Andrew Karaba[SUP] 1 [/SUP], Matthew Robinson[SUP] 1 4 [/SUP], Robin K Avery[SUP] 1 4 [/SUP], Paul Blair[SUP] 5 6 [/SUP], Natasha Chida[SUP] 1 4 [/SUP], Tania Jain[SUP] 7 [/SUP], Brent G Petty[SUP] 8 4 [/SUP], Zishan Siddiqui[SUP] 4 [/SUP], Michael T Melia[SUP] 1 4 [/SUP], Paul G Auwaerter[SUP] 1 [/SUP], Yanxun Xu[SUP] 3 [/SUP], Brian T Garibaldi[SUP] 9 [/SUP]
Affiliations
Abstract
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: 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: 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: 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.
Keywords: COVID-19; IL-6; SARS-CoV-2; retrospective; tocilizumab.
. 2020 Dec 28;8(1)
faa598.doi: 10.1093/ofid/ofaa598. eCollection 2021 Jan.
Tocilizumab for the Treatment of COVID-19 Among Hospitalized Patients: A Matched Retrospective Cohort Analysis
Elisa H Ignatius[SUP] 1 2 [/SUP], Kunbo Wang[SUP] 2 3 [/SUP], Andrew Karaba[SUP] 1 [/SUP], Matthew Robinson[SUP] 1 4 [/SUP], Robin K Avery[SUP] 1 4 [/SUP], Paul Blair[SUP] 5 6 [/SUP], Natasha Chida[SUP] 1 4 [/SUP], Tania Jain[SUP] 7 [/SUP], Brent G Petty[SUP] 8 4 [/SUP], Zishan Siddiqui[SUP] 4 [/SUP], Michael T Melia[SUP] 1 4 [/SUP], Paul G Auwaerter[SUP] 1 [/SUP], Yanxun Xu[SUP] 3 [/SUP], Brian T Garibaldi[SUP] 9 [/SUP]
Affiliations
- PMID: 33537364
- PMCID: PMC7798657
- DOI: 10.1093/ofid/ofaa598
Abstract
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: 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: 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: 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.
Keywords: COVID-19; IL-6; SARS-CoV-2; retrospective; tocilizumab.