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Signals were broadly positive for months, but never definitive: the tocilizumab story.
Cozzi-Lepri, Alessandro; Smith, Colette; Mussini, Cristina.
  • Cozzi-Lepri A; Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, UCL, London, UK. Electronic address: a.cozzi-lepri@ucl.ac.uk.
  • Smith C; Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, UCL, London, UK.
  • Mussini C; Department of Infectious Diseases, Azienda Ospedaliero-Universitaria Policlinico of Modena, Modena, Italy.
Clin Microbiol Infect ; 28(3): 371-374, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1509691
ABSTRACT

BACKGROUND:

Most treatment guidelines for coronavirus disease 2019 (COVID-19) currently recommend tocilizumab in combination with dexamethasone in critically ill patients who are exhibiting rapid respiratory decompensation.

AIMS:

To produce a critical review and summary of the pathway which led to the repurposing of tocilizumab for COVID-19 treatment, from in vitro observations to guidelines recommendations. SOURCES All studies evaluating the effectiveness of tocilizumab to treat COVID-19 disease published between July 2020 and July 2021. CONTENT Two large and methodologically well conducted observational studies, the TESEO and the STOP COVID cohorts, showed a reduction in the risk of invasive mechanical ventilation or death in patients treated with tocilizumab as compared to standard of care in 2020. Concomitantly, and up to February 2021, a number of randomized trials (RCTs) with small sample sizes were showing discrepant results. These RCTs had a number of issues small sample size, various designs and inclusion criteria, and different dosages of tocilizumab used. The confidence interval of the meta-analytic estimate for the RCT results was consistent with the hypothesis of no efficacy of tocilizumab. In our opinion, this was mainly because the meta-analysis included small and heterogeneous studies. These results led to a delay in the inclusion of tocilizumab in guidelines which occurred only in the summer of 2021. IMPLICATIONS Although observational studies are unable to control for unmeasured confounding, they can be put together quickly during a pandemic and promptly provide important information. The large sample size allows us to investigate effect measure modifiers and to better target interventions. It is key that the effect size is somewhat large (RR > 2), all sources of bias are properly accounted for, and the direct evidence is weighted against these factors. It appears to us that for tocilizumab, not having dismissed the results of carefully designed and analysed observational studies in 2020 could have prevented many deaths over those months.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Drug Treatment Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study / Randomized controlled trials / Reviews Limits: Humans Language: English Journal: Clin Microbiol Infect Journal subject: Communicable Diseases / Microbiology Year: 2022 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Drug Treatment Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study / Randomized controlled trials / Reviews Limits: Humans Language: English Journal: Clin Microbiol Infect Journal subject: Communicable Diseases / Microbiology Year: 2022 Document Type: Article