Interleukin-6 receptor blocking with intravenous tocilizumab in COVID-19 severe acute respiratory distress syndrome: A retrospective case-control survival analysis of 128 patients

Canziani, Lorenzo Maria; Trovati, Serena; Brunetta, Enrico; Testa, Amidio; Santis, Maria De; Bombardieri, Emilio; Guidelli, Giacomo Maria; Albano, Giovanni; Folci, Marco; Squadroni, Michela; Beretta, Giordano Domenico; Ciccarelli, Michele; Castoldi, Massimo; Lleo, Ana; Aghemo, Alessio; Vernile, Laura; Malesci, Alberto; Omodei, Paolo; Angelini, Claudio; Badalamenti, Salvatore; Cecconi, Maurizio; Cremonesi, Alberto; Selmi, Carlo

doi:10.1016/j.jaut.2020.102511

Cited by 81 publications

(93 citation statements)

References 35 publications

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“…For example, Optimal COVID-19 infection management with TCZ is not achieved during hyperglycaemia in both diabetic and non-diabetic patients that TCZ administration neither decreases IL-6 levels nor attenuates risk of severe outcomes (55). Similarly, the use of TCZ fails to decrease the mortality rate at 30 days of patients with severe COVID-19 acute respiratory distress syndrome with hyperinflammation, after correction for pre-existing comorbidities and the need for respiratory support (56). In addition, adverse reactions of TCZ in other long-course treatments need to be noted.…”

Section: Discussionmentioning

confidence: 99%

Tocilizumab: The Key to Stop Coronavirus Disease 2019 (COVID-19)-Induced Cytokine Release Syndrome (CRS)?

et al. 2020

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The COVID-19 disease is an unprecedented international public health emergency and considerably impacts the global economy and health service system. While awaiting the development of an effective vaccine, searching for the therapy for severe or critical COVID-19 patients is essential for reducing the mortality and alleviating the tension of the health service system. Cytokine release syndrome (CRS) induced by elevated interleukin-6 was recognized to underscore the pathology of severe COVID-19 patients. Inhibiting CRS by agents suppressing IL-6 may relieve symptoms, shorten the hospital stay and reduce the need for oxygen therapy. Although evidence from randomized, double-blinded clinical trials is still lacking, the IL-6R inhibitor tocilizumab (TCZ) has shown some clinical benefits in the treatment of severe COVID-19 patients and have been included in clinical guidelines. In this review, we focused on the possible mechanisms of TCZ in the treatment of CRS and highlighted some significant considerations in the use of TCZ to treat COVID-19 patients.

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Section: Discussionmentioning

confidence: 99%

Tocilizumab: The Key to Stop Coronavirus Disease 2019 (COVID-19)-Induced Cytokine Release Syndrome (CRS)?

et al. 2020

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“…In addition, several retrospective case-control studies on the use of tocilizumab in COVID-19 have been published ( 121 – 126 ), of which a majority reported a favorable outcome of tocilizumab treatment compared to controls. Of these, Campochiaro et al and Canziani et al did not find a statistically reduced mortality in tocilizumab treated patients, although both studies showed a respective trend ( 121 , 122 ) additionally, tocilizumab treated patients required invasive ventilation statistically less frequently than controls ( 122 ). In line with this observation the outcomes of several studies suggest that patients may benefit most from tocilizumab if given before invasive ventilation ( 125 , 127 ).…”

Section: Should We Use Dmards For the Therapy Of Covid-19?mentioning

confidence: 92%

Rheumatic Musculoskeletal Diseases and COVID-19 A Review of the First 6 Months of the Pandemic

et al. 2020

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In December 2019, a cluster of severe pneumonia was observed in China, with the subsequent discovery of a new beta-coronavirus (SARS-CoV-2) as the causative agent. The elicited disease COVID-19 is characterized by fever, dry cough, myalgia, or fatigue and has a favorable outcome in the majority of cases. However, in some patients COVID-19 leads to severe pneumonia and sepsis with subsequent respiratory failure and gastrointestinal, hematological, neurological, and cardiovascular complications. A higher risk of infection is intrinsic to active rheumatic and musculoskeletal diseases (RMD) and the use of biological disease modifying anti-rheumatic drugs (DMARDs). With an increasing number of reports on COVID-19 in RMD patients, we are beginning to appraise their risks. In this review, we summarize the published cases of COVID-19 infections in RMD patients, including patients with inflammatory arthritis and connective tissue diseases as well as anti-phospholipid syndrome and Kawasaki syndrome. Overall, patients with inflammatory arthritis do not seem to be at a higher risk for infection or a severe course of COVID-19. Risk for critical COVID-19 in patients with systemic inflammatory diseases such as SLE or vasculitis might be increased, but this needs further confirmation. Furthermore, we summarize the data on DMARDs used to fight SARS-CoV-2 infection and hyperinflammation.

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“…The total (random effects) synthesizes data from the 16 individual case-control studies. significance (Colaneri et al, 2020;Roumier et al, 2020;Guaraldi et al, 2020;Canziani et al, 2020) (Table S1). Only one study (Colaneri et al, 2020) provided both baseline and post-treatment values for biomarkers such as IL-6, CRP, lymphocytes, neutrophils, ALT etc.…”

Section: Figurementioning

confidence: 99%

“…5) and the number of patients in the meta-analysis exceeded the 392 required total case and control patients to statistically detect the difference in mortality rate. Some studies also secondarily investigated the rate of ICU admission with nine finding a lower rate with TCZ vs SOC and four having statistical significance (Colaneri et al, 2020;Roumier et al, 2020;Guaraldi et al, 2020;Canziani et al, 2020) (Table S1). Although the value of any single controlled clinical study does not hold definitive proof of efficacy, the consistent positive trend and statistical significance from the combined data in this analysis corroborates TCZ's potential positive effects.…”

Section: Mortalitiesmentioning

confidence: 99%

The efficacy of IL-6 inhibitor Tocilizumab in reducing severe COVID-19 mortality: a systematic review

Kaye

Siegel

2020

PeerJ

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Background In the absence of highly effective antiviral therapies against SARS-CoV-2, it is crucial to counter the known pathophysiological causes of severe COVID-19. Evaluating the efficacy existing drugs may expedite the development of such therapeutics. Severe COVID-19 is largely the result of a dysregulated immune response characterized by lymphocytopenia, neutrophilia and critical hypercytokinemia, or “cytokine storm,” which is largely mediated by the cytokine interleukin-6 (IL-6). The IL-6 inhibitor tocilizumab (TCZ) could potentially suppress the effects of the pro-inflammatory cytokine and thereby lower mortality from the disease. This systematic analysis aimed to investigate and synthesize existing evidence for the efficacy of TCZ in reducing COVID-19 mortality. Methodology PubMed and SearchWorks searches were performed to locate clinical studies with primary data on TCZ treatment for severe COVID-19. Sixteen case-control studies comparing mortality between TCZ and standard of care (SOC) were identified for quantitative synthesis. The systematic analysis was pre-approved through PROSPERO (CRD42020193479). Results Combined mortality for the TCZ-treated and SOC groups were 26.0% and 43.4% respectively. In all but one of the studies, the odds ratio of mortality from COVID-19 pointed towards lower fatality with TCZ vs the SOC. A combined random effects odds ratio calculation yielded an odds ratio of 0.453 (95% CI [0.376–0.547], p < 0.001). Additionally, 18 uncontrolled trials were identified for qualitative analysis producing a raw combined mortality rate of 16.0%. Conclusions Important caveats to this research include the lack of prospective randomized control trials and the absence of data from the large COVATA study from the published literature. However, results from this systematic analysis of published research provide positive evidence for the potential efficacy of TCZ to treat severe COVID-19, validating the ethical basis and merit of ongoing randomized controlled clinical trials.

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Interleukin-6 receptor blocking with intravenous tocilizumab in COVID-19 severe acute respiratory distress syndrome: A retrospective case-control survival analysis of 128 patients

Cited by 81 publications

References 35 publications

Tocilizumab: The Key to Stop Coronavirus Disease 2019 (COVID-19)-Induced Cytokine Release Syndrome (CRS)?

Tocilizumab: The Key to Stop Coronavirus Disease 2019 (COVID-19)-Induced Cytokine Release Syndrome (CRS)?

Rheumatic Musculoskeletal Diseases and COVID-19 A Review of the First 6 Months of the Pandemic

The efficacy of IL-6 inhibitor Tocilizumab in reducing severe COVID-19 mortality: a systematic review

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