Tocilizumab in COVID-19: Factors Associated With Mortality Before and After Treatment

Ardanaz, Luis Sarabia de; Andreu-Ubero, Jose M; Navidad-Fuentes, Miriam; Ferrer-González, Miguel Ángel; Valle, Victor Ruíz Del; Salcedo‐Bellido, Inmaculada; Barrios‐Rodríguez, Rocío; Cáliz-Cáliz, Rafael; Requena, Pilar

doi:10.3389/fphar.2021.620187

Cited by 11 publications

(33 citation statements)

References 51 publications

(85 reference statements)

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“…Deceased patients had significantly lower lymphocyte counts than surviving patients, which was consistent with other cohorts that reported the same observation [32,39], one without statistical analysis [32]. Some studies reported a direct relation between blood fibrinogen level and mortality of COVID-19 patients on tocilizumab [32,39]. However, this element was not assessed in our study.…”

Section: Discussionsupporting

confidence: 91%

“…Similarly to what was reported by other studies, there was an inverse relationship between platelet count and the mortality of COVID-19 patients on tocilizumab [32,39]. Deceased patients had significantly lower lymphocyte counts than surviving patients, which was consistent with other cohorts that reported the same observation [32,39], one without statistical analysis [32]. Some studies reported a direct relation between blood fibrinogen level and mortality of COVID-19 patients on tocilizumab [32,39].…”

Section: Discussionsupporting

confidence: 87%

“…Though our study results illustrated that the nonsurvivor group had a significantly higher number of patients who reported having hypertension, cardiac diseases, DM, arthritis, cancer, and osteopenia/osteoporosis, other studies reported DM and cancer only [31,32], while other studies found no significant differences in comorbidities between survival and nonsurvival patients [30]. The current study's results indicated that admission to ICUs increased the probability of death due to COVID-19 infection, which was not seen by other studies [30,32]. However, some studies excluded patients admitted to ICUs from their analysis [39].…”

Section: Discussioncontrasting

confidence: 72%

“…However, no statistical analysis was conducted to see the significance of the changes from the baseline, and the study was limited by its small sample size (n = 27) [30]. Similarly, Arandaz et al [32] assessed the effect of tocilizumab after 3, 6, and 9 days of administration on survived vs. deceased patients (n = 120, one dose = 90, two doses = 20, and three doses = 2), and based on the presented graphs (no values with no statistical analysis in comparison to the baseline), after 9 days of tocilizumab administration, there were decreases in IL-6, CRP, and LDH levels and almost no change in neutrophile and platelets counts in the survived patients. In contrast, deceased patients showed increased IL-6, CRP, LDH, and neutrophil and platelet counts on the ninth day of tocilizumab administration.…”

Section: Discussionmentioning

confidence: 99%

“…Many studies have discussed clinical characteristics and predictors of mortality in COVID-19 patients worldwide [ 21 , 22 , 23 , 24 , 25 , 26 ] and in Saudi Arabia specifically [ 27 , 28 , 29 ]. However, our study was one of the few that assessed these predictors in COVID-19 patients receiving tocilizumab [ 30 , 31 , 32 ] and the first one in Saudi Arabia. Furthermore, our study was considered the largest retrospective study in terms of the number of patients (300 patients), and the largest study ever in the number of assessed parameters (74 group variables with 107 individual variables), that investigated the predictors of mortality in COVID-19 patients on tocilizumab.…”

Section: Discussionmentioning

confidence: 99%

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Safety of Tocilizumab in COVID-19 Patients and Benefit of Single-Dose: The Largest Retrospective Observational Study

et al. 2022

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Severe acute respiratory coronavirus-2 (SARS-CoV-2) still presents a public threat and puts extra strain on healthcare facilities. Without an effective antiviral drug, all available treatment options are considered supportive. Tocilizumab as a treatment option has to date shown variable results. In this retrospective study, we aimed to assess predictors of mortality of COVID-19 patients (n = 300) on tocilizumab and the clinical effectiveness of this drug. The results showed that ICU admission OR = 64.6 (95% CI: 8.2, 507.4); age of the patient OR = 1.1 (95% CI: 1.0, 1.1); and number of tocilizumab doses administered by the patient OR(two doses) = 4.0 (95% CI: 1.5, 10.9), OR(three doses) = 1.5 (95% CI: 0.5, 5.1), and OR(four doses or more) = 7.2 (95% CI: 2.0, 25.5) presented strong correlation factors that may be linked to COVID-19 mortality. Furthermore, our study showed the beneficial effects of early administration of tocilizumab OR = 1.2 (95% CI: 1.1, 1.4) and longer hospital length of stay OR = 0.974 (95% CI: 0.9, 1.0) in reducing COVID-19 mortalities. High blood D-dimer concentration OR = 1.1 (95% CI: 1.0, 1.2) and reciprocal blood phosphate concentration OR = 0.008 (95% CI: 0.0, 1.2) were correlated to high mortality under SARS-CoV-2 infection. The short-term effect of a single dose of tocilizumab was a significant increase in blood BUN and liver enzymes (ALT, AST, and LDH) above their normal ranges. Furthermore, it significantly reduced CRP blood concentration, but not to normal levels (13.90 to 1.40 mg/dL, p < 0.001). Assessing the effect of different doses of tocilizumab (in terms of the number of doses, total mg, and total mg/kg administered by the patients) indicated that administering more than one dose may lead to increases in ICU length of stay and hospital length of stay of up to 14 and 22 days after the last dose of tocilizumab (6 to 14, p = 0.06, and 10 to 22, p < 0.001), with no improvement in 28- and 90-day mortality, as confirmed by Kaplan–Meier analysis. There were also clear correlations and trends between the number of doses of tocilizumab and increased blood CO2, MCV, RDW, and D-dimer concentrations and between number of doses of tocilizumab and decreased CRP, AST, and hemoglobin concentrations. Microbiology analysis showed a significant increase in the incidence of infection after tocilizumab administration (28 to 119, p < 0.001) with a median time of incidence within 6 days of the first dose of tocilizumab. A significant correlation was also found between the number of tocilizumab doses and the number of incidences of infections after tocilizumab administration r (298) = 0.396, p = 1.028 × 10−12. Based on these results and depending on the pharmacokinetic parameters of the drug, we recommend single-dose administration of tocilizumab as the optimal dosage for COVID-19 patients who do not have active bacterial infection or liver diseases, to be administered as soon as the patient is admitted to the hospital.

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