Tocilizumab in the treatment of critical COVID-19 pneumonia: A retrospective cohort study of mechanically ventilated patients

Fisher, M.; Raymundo, Luis A Marcos; Monteforte, Melinda; Taub, Erin; Go, Roderick

doi:10.1016/j.ijid.2020.12.021

Cited by 24 publications

(23 citation statements)

References 12 publications

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“…The PRISMA flow diagram is detailed in Figure 1. The majority of included studies were carried out in different hospitals from countries in America and Europe, such as the United States (US) 46,47,[51][52][53][54][55]61,67,68,70,76,82,84,[86][87][88][89][90]92,94 , Italy (ITA) 41,[43][44][45]48,49,58,60,69,77,79,91,95 , Spain (SPA) 40,42,63,64,71,75,78,83,85 , and France (FRA). 56,57,59,62,96 A lesser number was conducted in Sweden (SWE) 50 , India (IND)…”

Section: Re Sultsmentioning

confidence: 99%

Beneficial and harmful outcomes of tocilizumab in severe COVID‐19: A systematic review and meta‐analysis

et al. 2021

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Introduction:The results of studies of tocilizumab (TCZ) in COVID-19 are contradictory. Our study aims to update medical evidence from controlled observational studies and randomized clinical trials (RCTs) on the use of TCZ in hospitalized patients with COVID-19. Methods:We searched the following databases from January 1, 2020 to April 13, 2021 (date of the last search): MEDLINE database through the PubMed search engine and Scopus, using the terms ("COVID-19" [Supplementary Concept]) AND "tocilizumab" [Supplementary Concept]).Results: Sixty four studies were included in the present study: 54 were controlled observational studies (50 retrospective and 4 prospective) and 10 were RCTs. The overall results provided data from 20,616 hospitalized patients with COVID-19: 7668 patients received TCZ in addition to standard of care (SOC) (including 1915 patients admitted to intensive care units (ICU) with reported mortality) and 12,948 patients only receiving SOC (including 4410 patients admitted to the ICU with reported mortality). After applying the random-effects model, the hospital-wide (including ICU) pooled mortality odds ratio (OR) of patients with COVID-19 treated with TCZ was 0.73 (95% confidence interval (CI) = 0.56-0.93). The pooled hospital-wide mortality OR was 1.25 (95% CI = 0.74-2.18) in patients admitted at conventional wards versus 0.66 (95% CI = 0.59-0.76) in patients admitted to the ICU. The pooled OR of hospitalwide mortality (including ICU) of COVID-19 patients treated with TCZ plus corticosteroids (CS) was 0.67 (95% CI = 0.54-0.84). The pooled in-hospital mortality OR was 0.71 (95% CI = 0.35-1.42) when TCZ was early administered (≤10 days from symptom onset) versus 0.83 (95% CI 0.48-1.45) for late administration (>10 days from symptom onset). The meta-analysis did not find significantly higher risk for secondary infections in COVID-19 patients treated with TCZ.Conclusions: TCZ prevented mortality in patients hospitalized for COVID-19. This benefit was seen to a greater extent in patients receiving concomitant CS and when TCZ administration occurred within the first 10 days after symptom onset.

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Section: Re Sultsmentioning

confidence: 99%

Beneficial and harmful outcomes of tocilizumab in severe COVID‐19: A systematic review and meta‐analysis

et al. 2021

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“…When tocilizumab was administered in patients with critical illness necessitating ICU admission results were not that promising. Two retrospective analyses, one including 45 mechanically ventilated patients treated with tocilizumab and 70 comparators (23) and another including 210 ICU patients treated with tocilizumab and 420 comparators (24) did not show any survival benefit. Another retrospective analysis of 45 severe/critical patients used a primary endpoint much similar to ours i.e.…”

Section: Discussionmentioning

confidence: 94%

ESCAPE: An Open-Label Trial of Personalized Immunotherapy in Critically Ill COVID-19 Patients

Karakike¹,

Dalekos

Koutsodimitropoulos³

et al. 2021

Preprint

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RationaleMacrophage activation syndrome (MAS) and complex immune dysregulation (CID) often underlie acute respiratory distress (ARDS) in COVID-19.ObjectiveTo investigate the outcome of personalized immunotherapy in critical COVID-19.MethodsIn this open-label prospective trial, 102 patients with SOFA (sequential organ failure assessment) score ≥2 or ARDS by SARS-CoV-2 were screened for MAS (ferritin more than 4420 ng/ml) and CID (ferritin ≤4420 ng/ml and low expression of HLA-DR on CD14-monocytes). Patients with MAS and CID with increased aminotransferases were assigned to intravenous anakinra; those with CID and normal aminotransferases to tocilizumab. The primary outcome was at least 25% decrease of SOFA score and/or 50% increase of respiratory ratio by day 8; 28-day mortality, change of SOFA score by day 28; serum biomarkers and cytokine production by mononuclear cells were secondary endpoints.Measurements and Main ResultsThe primary study endpoint was met in 58.3% of anakinra-treated patients and in 33.3% of tocilizumab-treated patients (odds ratio 3.11; 95% CIs 1.29-7.73; P: 0.011). No differences were found in mortality and in SOFA score changes. By day 4, ferritin was decreased among anakinra-treated patients; interleukin (IL)-6, soluble urokinase plasminogen activator receptor (suPAR) and the expression of HLA-DR were increased among tocilizumab-treated patients. Anakinra increased capacity of mononuclear cells to produce IL-6. Survivors by day 28 who received anakinra were distributed to scales of the WHO clinical progression of lower severity. Greater incidence of secondary infections was found with tocilizumab treatment.ConclusionsBiomarkers may guide favourable anakinra responses in critically ill patients with COVID-19.Trial RegistrationClinicalTrials.gov, NCT04339712

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“…A total of 47 studies, 40 observational studies [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 ] reported in Table 2 and 7 RCTs [ 66 , 67 , 68 , 69 , 70 , 71 , 72 ] reported in Table 3 , were included in the final analysis.…”

Section: Resultsmentioning

confidence: 99%

“…Overall, a significant effect in reducing the death rates was found by analyzing the studies [ 35 , 47 , 51 , 57 , 62 , 65 ] evaluating critically ill patients receiving IMV when TCZ was administered.…”

Section: Discussionmentioning

confidence: 99%

Effect of Tocilizumab in Reducing the Mortality Rate in COVID-19 Patients: A Systematic Review with Meta-Analysis

Conti

Corbi

Sellitto

et al. 2021

JPM

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Data supporting the use of Tocilizumab (TCZ) in COVID-19 are contrasting and inconclusive. This meta-analysis aimed to assess TCZ effectiveness in reducing the mortality rate in COVID-19 patients. PubMed, Scopus, Embase, Cochrane, WILEY, and ClinicalTrials.gov were searched to evaluate observational studies and RCTs. The outcome was the mortality rate. Forty observational studies and seven RCTs, involving 9640 and 5556 subjects treated with Standard Therapy (ST) + TCZ or ST alone, respectively, were included. In patients treated with ST+TCZ, a higher survival (Log odds ratio = −0.41; 95% CI: −0.68 −0.14; p < 0.001) was found. Subgroups analyses were performed to better identify the possible interference of some parameters in modifying the efficacy of TCZ therapy on COVID-19 mortality. Separating observational from RCTs, no statistically significant (p = 0.70) TCZ-related reduction of mortality regarding RCTs was found, while a significant reduction (Log odds ratio = −0.52; 95% CI: −0.82 −0.22, p < 0.001) was achieved regarding the observational studies. Stratifying for the use of Invasive Mechanic Ventilation (IMV), a higher survival was found in patients treated with TCZ in the No-IMV and IMV groups (both p < 0.001), but not in the No-IMV/IMV group. Meta-regression analyses were also performed. The meta-analysis of observational studies reveals that TCZ is associated with reducing the mortality rate in both severe and critically ill patients. Although the largest RCT, RECOVERY, is in line with this result, the meta-analysis of RCTs failed to found any difference between ST + TCZ and ST. It is crucial to personalize the therapy considering the patients’ characteristics.

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Tocilizumab in the treatment of critical COVID-19 pneumonia: A retrospective cohort study of mechanically ventilated patients

Cited by 24 publications

References 12 publications

Beneficial and harmful outcomes of tocilizumab in severe COVID‐19: A systematic review and meta‐analysis

Beneficial and harmful outcomes of tocilizumab in severe COVID‐19: A systematic review and meta‐analysis

ESCAPE: An Open-Label Trial of Personalized Immunotherapy in Critically Ill COVID-19 Patients

Effect of Tocilizumab in Reducing the Mortality Rate in COVID-19 Patients: A Systematic Review with Meta-Analysis

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