Evidence map›Paper›PMID 34768021›Full record

SynthesisClinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases2022

Signals were broadly positive for months, but never definitive: the tocilizumab story.

Alessandro Cozzi-Lepri, Colette Smith, Cristina Mussini

Open access · bronzeAbstract readMeta-AnalysisReview
In one paragraph

Synthesis in Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
0.1field-weighted citation impact, top 56% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed, 1 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 2 countries.

Alessandro Cozzi-LepriCentre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, UCL, London, UK. Electronic address: a.cozzi-lepri@ucl.ac.uk.
Colette SmithCentre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, UCL, London, UK.
Cristina MussiniDepartment of Infectious Diseases, Azienda Ospedaliero-Universitaria Policlinico of Modena, Modena, Italy.
National Institute for Health Research · GBAzienda Ospedaliero-Universitaria di Modena · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMost 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.

aimsTo 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.

Indexed as

COVID-19 Drug TreatmentAntibodies, Monoclonal, HumanizedHumansSARS-CoV-2Antibodies, Monoclonal, HumanizedtocilizumabCovid-19Evidence-based medicineMeta-analysisPropensity score methodsTocilizumab

Identifiers

PMID34768021
PMCPMC8576060
OpenAlexW3213833008

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.