Time for tocilizumab in COVID-19?

Butler, Ethan; Munch, Marie Warrer; Venkatesh, Balasubramanian

doi:10.1007/s00134-021-06441-y

Cited by 8 publications

(7 citation statements)

References 16 publications

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“…Thus, it is important to better understand the role of tocilizumab in combination with remdesivir and other treatments, including newer antivirals, neutralizing antibodies, and other immunomodulators. Additional studies or patient-level meta-analyses may be required to achieve this [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Tocilizumab and remdesivir in hospitalized patients with severe COVID-19 pneumonia: a randomized clinical trial

et al. 2021

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Purpose Trials of tocilizumab in patients with severe COVID-19 pneumonia have demonstrated mixed results, and the role of tocilizumab in combination with other treatments is uncertain. Here we evaluated whether tocilizumab plus remdesivir provides greater benefit than remdesivir alone in patients with severe COVID-19 pneumonia. Methods This randomized, double-blind, placebo-controlled, multicenter trial included patients hospitalized with severe COVID-19 pneumonia requiring > 6 L/min supplemental oxygen. Patients were randomly assigned (2:1 ratio) to receive tocilizumab 8 mg/kg or placebo intravenously plus ≤ 10 days of remdesivir. The primary outcome was time from randomization to hospital discharge or “ready for discharge” (defined as category 1, assessed by the investigator on a 7-category ordinal scale of clinical status) to day 28. Patients were followed for 60 days. Results Among 649 enrolled patients, 434 were randomly assigned to tocilizumab plus remdesivir and 215 to placebo plus remdesivir. 566 patients (88.2%) received corticosteroids during the trial to day 28. Median time from randomization to hospital discharge or “ready for discharge” was 14 (95% CI 12–15) days with tocilizumab plus remdesivir and 14 (95% CI 11–16) days with placebo plus remdesivir [log-rank P = 0.74; Cox proportional hazards ratio 0.97 (95% CI 0.78–1.19)]. Serious adverse events occurred in 128 (29.8%) tocilizumab plus remdesivir and 72 (33.8%) placebo plus remdesivir patients; 78 (18.2%) and 42 (19.7%) patients, respectively, died by day 28. Conclusions Tocilizumab plus remdesivir did not shorten time to hospital discharge or “ready for discharge” to day 28 compared with placebo plus remdesivir in patients with severe COVID-19 pneumonia. Supplementary Information The online version contains supplementary material available at 10.1007/s00134-021-06507-x.

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Section: Discussionmentioning

confidence: 99%

Tocilizumab and remdesivir in hospitalized patients with severe COVID-19 pneumonia: a randomized clinical trial

et al. 2021

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“…20,26 Local guidelines for the use of non-invasive ventilation and highflow nasal oxygen and concerns about the risk of contamination by aerosols, as well as the availability of intermediate care units for the provision of non-invasive respiratory support may explain these differences. With limited data available on risks and benefits of various pharmacological interventions, a substantial use of medications with unknown effectiveness (antiviral therapy, IL-6 antagonists) 6,8,27 and medications later found to be harmful (azithromycin, hydroxychloroquine) 28 respectively. 30 Overall, there has been a trend towards lower ICU mortality later in the pandemic, 30,31 33 The primary strength of the study is the inclusion in all countries of all COVID-19 patients admitted to ICU, minimizing the risk of bias.…”

Section: Discussionmentioning

confidence: 99%

A descriptive study of the surge response and outcomes of ICU patients with COVID‐19 during first wave in Nordic countries

Chew

Kattainen

Haase

et al. 2021

Acta Anaesthesiol Scand

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Background We sought to provide a description of surge response strategies and characteristics, clinical management and outcomes of patients with severe COVID‐19 in the intensive care unit (ICU) during the first wave of the pandemic in Denmark, Finland, Iceland, Norway and Sweden. Methods Representatives from the national ICU registries for each of the five countries provided clinical data and a description of the strategies to allocate ICU resources and increase the ICU capacity during the pandemic. All adult patients admitted to the ICU for COVID‐19 disease during the first wave of COVID‐19 were included. The clinical characteristics, ICU management and outcomes of individual countries were described with descriptive statistics. Results Most countries more than doubled their ICU capacity during the pandemic. For patients positive for SARS‐CoV‐2, the ratio of requiring ICU admission for COVID‐19 varied substantially (1.6%–6.7%). Apart from age (proportion of patients aged 65 years or over between 29% and 62%), baseline characteristics, chronic comorbidity burden and acute presentations of COVID‐19 disease were similar among the five countries. While utilization of invasive mechanical ventilation was high (59%–85%) in all countries, the proportion of patients receiving renal replacement therapy (7%–26%) and various experimental therapies for COVID‐19 disease varied substantially (e.g. use of hydroxychloroquine 0%–85%). Crude ICU mortality ranged from 11% to 33%. Conclusion There was substantial variability in the critical care response in Nordic ICUs to the first wave of COVID‐19 pandemic, including usage of experimental medications. While ICU mortality was low in all countries, the observed variability warrants further attention.

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“…Similarly, the Bayesian reanalysis of RECOVERY trial showed that probabilities for a clinically significant mortality reduction (absolute risk difference > 3%) were 77%, 96%, and 56% in patients on simple oxygen, NIV, and iMV, respectively [ 14 ]. Taken together, the immunomodulatory effect of IL6-RAs and steroid appears to be most beneficial shortly following clinical deterioration at systemic hyper-inflammation onset and ideally before intubation, as their effect appears to be less pronounced if administered late for subsets of patients with iMV [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical characteristics and outcomes of critically ill mechanically ventilated COVID-19 patients receiving interleukin-6 receptor antagonists and corticosteroid therapy: a preliminary report from a multinational registry

et al. 2021

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Background Interleukin-6 receptor antagonists (IL-6RAs) and steroids are emerging immunomodulatory therapies for severe and critical coronavirus disease (COVID-19). In this preliminary report, we aim to describe the epidemiology, clinical characteristics, and outcomes of adult critically ill COVID-19 patients, requiring invasive mechanical ventilation (iMV), and receiving IL-6RA and steroids therapy over the last 11 months. Materials and methods International, multicenter, cohort study derived from Viral Infection and Respiratory Illness University Study registry and conducted through Discovery Network, Society of Critical Care Medicine. Data were collected between March 01, 2020, and January 10, 2021. Results Of 860 patients who met eligibility criteria, 589 received steroids, 170 IL-6RAs, and 101 combinations. Patients who received IL-6RAs were younger (median age of 57.5 years vs. 61.1 and 61.8 years in the steroids and combination groups, respectively). The median C-reactive protein level was > 75 mg/L, indicating a hyperinflammatory phenotype. The median daily steroid dose was 7.5 mg dexamethasone or equivalent (interquartile range: 6–14 mg); 80.8% and 19.2% received low-dose and high-dose steroids, respectively. Of the patients who received IL-6RAs, the majority received one dose of tocilizumab and sarilumab (dose range of 600–800 mg for tocilizumab and 200–400 mg for sarilumab). Regarding the timing of administration, we observed that steroid and IL-6RA administration on day 0 of ICU admission was only 55.6% and 39.5%, respectively. By day 28, when compared with steroid use alone, IL-6RA use was associated with an adjusted incidence rate ratio (aIRR) of 1.12 (95% confidence interval [CI] 0.88, 1.4) for ventilator-free days, while combination therapy was associated with an aIRR of 0.83 (95% CI 0.6, 1.14). IL-6RA use was associated with an adjusted odds ratio (aOR) of 0.68 (95% CI 0.44, 1.07) for the 28-day mortality rate, while combination therapy was associated with an aOR of 1.07 (95% CI 0.67, 1.70). Liver dysfunction was higher in IL-6RA group (p = 0.04), while the bacteremia rate did not differ among groups. Conclusions Discordance was observed between the registry utilization patterns (i.e., timing of steroids and IL-6RA administration) and new evidence from the recent randomized controlled trials and guideline recommendations. These data will help us to identify areas of improvement in prescribing patterns and enhance our understanding of IL-6RA safety with different steroid regimens. Further studies are needed to evaluate the drivers of hospital-level variation and their impact on clinical outcomes. Trial registration ClinicalTrials.gov: NCT04486521. Registered on July 2020

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Time for tocilizumab in COVID-19?

Cited by 8 publications

References 16 publications

Tocilizumab and remdesivir in hospitalized patients with severe COVID-19 pneumonia: a randomized clinical trial

Tocilizumab and remdesivir in hospitalized patients with severe COVID-19 pneumonia: a randomized clinical trial

A descriptive study of the surge response and outcomes of ICU patients with COVID‐19 during first wave in Nordic countries

Clinical characteristics and outcomes of critically ill mechanically ventilated COVID-19 patients receiving interleukin-6 receptor antagonists and corticosteroid therapy: a preliminary report from a multinational registry

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