Tocilizumab among patients with COVID-19 in the intensive care unit: a multicentre observational study

Abstract

Background Tocilizumab, a monoclonal antibody directed against the interleukin-6 receptor, has been proposed to mitigate the cytokine storm syndrome associated with severe COVID-19. We aimed to investigate the association between tocilizumab exposure and hospital-related mortality among patients requiring intensive care unit (ICU) support for COVID-19. Methods We did a retrospective observational cohort study at 13 hospitals within the Hackensack Meridian Health network (NJ, USA). We included patients (aged ≥18 years) with laboratory-confirmed COVID-19 who needed support in the ICU. We obtained data from a prospective observational database and compared outcomes in patients who received tocilizumab with those who did not. We applied a multivariable Cox model with propensity score matching to reduce confounding effects. The primary endpoint was hospital-related mortality. The prospective observational database is registered on ClinicalTrials.gov , NCT04347993 . Findings Between March 1 and April 22, 2020, 764 patients with COVID-19 required support in the ICU, of whom 210 (27%) received tocilizumab. Factors associated with receiving tocilizumab were patients' age, gender, renal function, and treatment location. 630 patients were included in the propensity score-matched population, of whom 210 received tocilizumab and 420 did not receive tocilizumab. 358 (57%) of 630 patients died, 102 (49%) who received tocilizumab and 256 (61%) who did not receive tocilizumab. Overall median survival from time of admission was not reached (95% CI 23 days–not reached) among patients receiving tocilizumab and was 19 days (16–26) for those who did not receive tocilizumab (hazard ratio [HR] 0·71, 95% CI 0·56–0·89; p=0·0027). In the primary multivariable Cox regression analysis with propensity matching, an association was noted between receiving tocilizumab and decreased hospital-related mortality (HR 0·64, 95% CI 0·47–0·87; p=0·0040). Similar associations with tocilizumab were noted among subgroups requiring mechanical ventilatory support and with baseline C-reactive protein of 15 mg/dL or higher. Interpretation In this observational study, patients with COVID-19 requiring ICU support who received tocilizumab had reduced mortality. Results of ongoing randomised controlled trials are awaited. Funding None.

Prognostic factors in patients admitted to an urban teaching hospital with COVID-19 infection

“…Indeed, the role of dexamethasone is endorsed by the recent positive report from the RECOVERY trial that showed a significant survival benefit at 28-days among patients who required either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support [27]. Furthermore, there is emerging evidence of the importance of pro-inflammatory cytokines interleukin-6 (IL-6) and tumour necrosis factor (TNF-alpha) as predictors of mortality in patients with COVID-19 [28] and that IL-6 blockade appears to be beneficial [29]. Biran et alhave recently reported in a retrospective multi-centre observational study of 764 patients with severe SARS-CoV-2 infection requiring ICU support that treatment with a recombinant monoclonal antibody against the interleukin (IL)-6 receptor, Tocilizumab ® , was associated with a 25% reduction in hospital-related mortality [29].…”

“…Furthermore, there is emerging evidence of the importance of pro-inflammatory cytokines interleukin-6 (IL-6) and tumour necrosis factor (TNF-alpha) as predictors of mortality in patients with COVID-19 [28] and that IL-6 blockade appears to be beneficial [29]. Biran et alhave recently reported in a retrospective multi-centre observational study of 764 patients with severe SARS-CoV-2 infection requiring ICU support that treatment with a recombinant monoclonal antibody against the interleukin (IL)-6 receptor, Tocilizumab ® , was associated with a 25% reduction in hospital-related mortality [29]. Randomised trials are required to confirm these results.…”

Myeloid cell dynamics correlate with clinical outcomes of severe coronavirus disease 2019

“…Therefore, the period prior to the induction of acquired immunity might be a key decisive point for the clinical outcome of severe cases in which the control of viral replication without hyperin ammation is needed. Along the same line, it has been shown that the anti-in ammatory drugs dexamethasone and anti-IL-6 receptor monoclonal antibody reduce the mortality rate of severe COVID-19 cases [35][36][37][38] . We speculate that the emergence of the PMN-MDSC subset prolongs survival by suppressing excessive in ammation until acquired immunity is introduced.…”

<p>Current Options in the Treatment of COVID-19: A Review</p>

“…Baricitinib Inflammatory diseases, rheumatoid Arthritis 90,91 Reducing inflammatory responses, 90,91 having a greater efficiency in combination with RDV and LPV-RTV, 93 having the possibility of creating anemia 95,96 Corticosteroids (CSs) Inflammatory diseases 98 Reducing mortality, 102 having short-term or long-term side effects Anakinra Inflammatory diseases 108 Having good performance, reducing mortality, [110][111][112] Tocilizumab (TCZ) Inflammatory diseases, rheumatoid arthritis 116 Showing significant clinical progress, reducing inflammatory markers, reducing mortality, reducing the risk of invasive mechanical ventilation, improving oxygen delivery in patients, having few side effects [117][118][119][120][121][122][123] Anticoagulants Heparin Coagulation problems 130 Reducing mortality, 129 having side effects including drug resistance and heparin-induced thrombocytopenia (HIT) 130,131 Nafamostat mesylate Coagulation problems 134 Having the ability for in vitro inhibition of SARS-CoV-2 S protein-mediated cell fusion and its infection, [132][133][134] improving clinical conditions in patients in need of supplementary oxygen therapy. 135 Arbidol (ARB)…”

“…116 It has been reported that TCZ reduces mortality in patients with severe COVID-19. 117 A study was conducted in Italy on 100 patients with COVID-19 and ARDS to evaluate the effect of TCZ.…”