Tocilizumab Plus Dexamethasone in Patients with Moderate-to-Severe COVID-19 Pneumonia: a Randomized Clinical Trial of the CORIMUNO-19 Study Group

Hermine, Olivier; Mariette, Xavier; Tharaux, Pierre Louis; Resche‐Rigon, Matthieu; Simon, Tabassome; Porcher, Raphaël; Ravaud, Philippe

doi:10.2139/ssrn.3909736

Cited by 6 publications

(7 citation statements)

References 8 publications

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“…Among the 27 trials included in the meta-analyses, 9 were published [8][9][10][11][12][13][14]23,24 and the remaining 18 were unpublished or were reported as preprints (NCT04412772, NCT04331808 [there were 2 separate trials conducted under a common protocol], NCT04330638, NCT04479358, NCT04577534, NCT04435717, NCT04377750, NCT04409262, EU-CTR 2020-001748-24, EU-CTR 2020-001375-32, EU-CTR 2020-001442-19, NCT04324073 [there were 2 separate trials conducted under a common protocol], NCT04315298, NCT04357808, EU-CTR 2020-001531-27, and EU-CTR 2020-002037-15; Table 1 and eTables 1-3 in Supplement 1). Outcome data were supplied for 10 930 patients, representing 95.4% of all patients randomized in eligible trials (eFigure 1 in Supplement 1).…”

Section: Resultsmentioning

confidence: 99%

Association Between Administration of IL-6 Antagonists and Mortality Among Patients Hospitalized for COVID-19

Domingo

Mur

Mateo

et al. 2021

JAMA

558

387

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The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group IMPORTANCE Clinical trials assessing the efficacy of IL-6 antagonists in patients hospitalized for COVID-19 have variously reported benefit, no effect, and harm.OBJECTIVE To estimate the association between administration of IL-6 antagonists compared with usual care or placebo and 28-day all-cause mortality and other outcomes.DATA SOURCES Trials were identified through systematic searches of electronic databases between October 2020 and January 2021. Searches were not restricted by trial status or language. Additional trials were identified through contact with experts.STUDY SELECTION Eligible trials randomly assigned patients hospitalized for COVID-19 to a group in whom IL-6 antagonists were administered and to a group in whom neither IL-6 antagonists nor any other immunomodulators except corticosteroids were administered. Among 72 potentially eligible trials, 27 (37.5%) met study selection criteria. DATA EXTRACTION AND SYNTHESISIn this prospective meta-analysis, risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I 2 statistic. The primary analysis was an inverse variance-weighted fixed-effects meta-analysis of odds ratios (ORs) for 28-day all-cause mortality. MAIN OUTCOMES AND MEASURESThe primary outcome measure was all-cause mortality at 28 days after randomization. There were 9 secondary outcomes including progression to invasive mechanical ventilation or death and risk of secondary infection by 28 days.RESULTS A total of 10 930 patients (median age, 61 years [range of medians, 52-68 years]; 3560 [33%] were women) participating in 27 trials were included. By 28 days, there were 1407 deaths among 6449 patients randomized to IL-6 antagonists and 1158 deaths among 4481 patients randomized to usual care or placebo (summary OR, 0.86 [95% CI, 0.79-0.95]; P = .003 based on a fixed-effects meta-analysis). This corresponds to an absolute mortality risk of 22% for IL-6 antagonists compared with an assumed mortality risk of 25% for usual care or placebo. The corresponding summary ORs were 0.83 (95% CI, 0.74-0.92; P < .001) for tocilizumab and 1.08 (95% CI, 0.86-1.36; P = .52) for sarilumab. The summary ORs for the association with mortality compared with usual care or placebo in those receiving corticosteroids were 0.77 (95% CI, 0.68-0.87) for tocilizumab and 0.92 (95% CI, 0.61-1.38) for sarilumab. The ORs for the association with progression to invasive mechanical ventilation or death, compared with usual care or placebo, were 0.77 (95% CI, 0.70-0.85) for all IL-6 antagonists, 0.74 (95% CI, 0.66-0.82) for tocilizumab, and 1.00 (95% CI, 0.74-1.34) for sarilumab. Secondary infections by 28 days occurred in 21.9% of patients treated with IL-6 antagonists vs 17.6% of patients treated with usual care or placebo (OR accounting for trial sample sizes, 0.99; 95% CI, 0.85-1.16). CONCLUSIONS AND RELEVANCEIn this prospective meta-analysis of clinical trials of patients hosp...

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Section: Resultsmentioning

confidence: 99%

Association Between Administration of IL-6 Antagonists and Mortality Among Patients Hospitalized for COVID-19

Domingo

Mur

Mateo

et al. 2021

JAMA

558

387

View full text Add to dashboard Cite

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“…Hermine et al, 2021, set up that tocilizumab might lower the 14day but not one month mortality from hospitalization. So the series follow up of IL-6 serum level is crucial in deciding intervention timing of IL-6R inhibitors as elevated levels of specific cytokines such as IL-6 during the early stages of disease may contribute to multi organ damage [14] .…”

Section: Resultsmentioning

confidence: 99%

Efficacy Of Tocilizumab On Critical Intensive Care Unit COVID-19 Patients: Retrospective Study Among Egyptian Armed Forces Hospitals.

Hussien,

Fathi,

Mahmoud

et al. 2023

ARCADEs of MEDICINE

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Background: Since the first reports of COVID-19 disease, it has become clear that acute respiratory distress syndrome was responsible for a significant number of deaths among infected patients. Several studies have linked increased levels of proinflammatory cytokines in serum to pulmonary inflammation and extensive lung damage. Among proinflammatory cytokines, Interleukin-6 is the key cytokine that contributes to an inflammatory storm. Several studies have found that elevated IL-6 levels are associated with the severity of COVID-19 symptoms and death. Tocilizumab is monoclonal antibody that antagonizes the effect of IL-6. Early cytokine storm treatment may have benefits on COVID-19 patients' survival. Patients and Methods:The present study was conducted on 91 COVID-19 patients, admitted to intensive care unit and took tocilizumab. The IL-6 serum level data were collected from patients' files pre and post-tocilizumab administration. Regarding these data, we could determine the clinical outcome after treatment. Results: We demonstrated that there was a decrease in IL-6 serum level within both mild and moderate severity grades by 16.3% and 38.4% respectively, while there was a significant increase in the patients who had severe grade by 162%. There was a significant decrease in IL-6 serum level within recovered group by 66.1% and a significant increase within mortality group by 256% pre and post-injection with tocilizumab. Conclusion: IL-6 serum level may be a major indicator but not the sole driver in the pathology of COVID-19. So, when we assess IL-6 serum level, we should take into consideration other cytokines, and usage of combinations of many blockages for these cytokines may improve the outcome.

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“…Summary of evidence: The review identi ed 358 references, and 14 RCTs evaluating the effectiveness of tocilizumab in the population of interest were included [35][36][37][38][39][40][41][42][43][44][45][46][47]. The intervention used in the most prominent trial (RECOVERY) consisted of the intravenous infusion of a single tocilizumab dose of 800 mg if weight > 90 kg, 600 mg if weight > 65 and ≤ 90 kg, 400 mg if weight > 40 and ≤ 65 kg, or 8 mg/kg if weight ≤ 40 kg, and a second dose could be administered 12 to 24 hours later if, in the opinion of the clinician, the patient's condition had not improved [35].…”

Section: Hospitalised Patients With Covid-19mentioning

confidence: 99%

Pan-American Guidelines for the Treatment of SARS-CoV-2/COVID-19: A Joint Evidence-Based Guideline of the Brazilian Society of Infectious Diseases (SBI) and the Pan-American Association of Infectious Diseases (API)

Barbosa

Chebabo

Starling

et al. 2023

Preprint

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Background Since the beginning of the COVID-19 pandemic, therapeutic options for treating COVID-19 have been investigated at different stages of clinical manifestations. Considering the particular impact of COVID-19 in the Americas, this document aims to present recommendations for the pharmacological treatment of COVID-19 specific to this population. Method Fifteen experts, members of the Brazilian Society of Infectious Diseases (SBI) and the Pan-American Association of Infectious Diseases (API) make up the panel responsible for developing this guideline. Questions were formulated regarding prophylaxis and treatment of COVID-19 in outpatient and inpatient settings. The outcomes considered in decision-making were mortality, hospitalisation, need for mechanical ventilation, symptomatic COVID-19 episodes, and adverse events. In addition, a systematic review of randomised controlled trials was conducted. The quality of evidence assessment and guideline development process followed the GRADE system. Results Nine technologies were evaluated, and ten recommendations were made, including the use of tixagevimab + cilgavimab in the prophylaxis of COVID-19, tixagevimab + cilgavimab, molnupiravir, nirmatrelvir + ritonavir, and remdesivir in the treatment of outpatients, and remdesivir, baricitinib, and tocilizumab in the treatment of hospitalised patients with severe COVID-19. The use of hydroxychloroquine or chloroquine and ivermectin was discouraged. Conclusion This guideline provides recommendations for treating patients in the Americas following the principles of evidence-based medicine. The recommendations present a set of drugs that have proven effective in the prophylaxis and treatment of COVID-19, emphasising the strong recommendation for the use of nirmatrelvir/ritonavir in outpatients as the lack of benefit from the use of hydroxychloroquine and ivermectin.

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Tocilizumab Plus Dexamethasone in Patients with Moderate-to-Severe COVID-19 Pneumonia: a Randomized Clinical Trial of the CORIMUNO-19 Study Group

Cited by 6 publications

References 8 publications

Association Between Administration of IL-6 Antagonists and Mortality Among Patients Hospitalized for COVID-19

Association Between Administration of IL-6 Antagonists and Mortality Among Patients Hospitalized for COVID-19

Efficacy Of Tocilizumab On Critical Intensive Care Unit COVID-19 Patients: Retrospective Study Among Egyptian Armed Forces Hospitals.

Pan-American Guidelines for the Treatment of SARS-CoV-2/COVID-19: A Joint Evidence-Based Guideline of the Brazilian Society of Infectious Diseases (SBI) and the Pan-American Association of Infectious Diseases (API)

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