Survival and outcomes of tocilizumab use in severe and critically ill COVID-19 patients not responding to steroids

  1. Shiraz Assu
  2. Deepak Bhasin
  3. Kavita Sekhri
  4. Supriya Sampley
  5. Harpal Singh
  6. Gurleen Kaur

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Abstract

Background

Mortality and morbidity are highest in severe and critically ill patients with COVID -19 pneumonia. We used interleukin-6 (IL-6) receptor inhibitor, tocilizumab in the above patients who failed to show any clinical improvement after initial treatment with steroids.

Methods

This is a retrospective observational study conducted at a tertiary care hospital in India. Severe and critical COVID-19 patients, who got admitted to intensive care unit and subsequently received tocilizumab were included. Patients who worsened clinically or had no change in oxygen requirement even after 24hrs of receiving intravenous methylprednisolone at a dose of 1-2mg/kg/day received a maximum total dose of 800mg of intravenous tocilizumab. The day 28 all-cause mortality and progression to mechanical ventilation were the primary outcome measures. Clinical improvement and oxygen requirements after tocilizumab administration along with trends in inflammatory markers and secondary infections rates were also noted.

Results

A total of 51 patients who did not show clinical improvement even after 24 hours of intravenous steroids had received tocilizumab. In these patients, there was a significant decrease in oxygen requirement and clinical progression by day 7 of tocilizumab administration. Baseline median values of CRP (114.2 mg/L), IL-6 (69.8 pg/ml) and neutrophil-lymphocyte ratio (12.4) in these patients were elevated. Out of these, only CRP showed a significant decrease after the drug administration. 13 (26.5%) of the 49 patients on non-invasive oxygen support progressed to mechanical ventilation and the day 28 all-cause mortality was 10/51(19.6%). 10(19.6%) of the 51 patients had life threatening infections.

Conclusion

Early and timely administration of tocilizumab is a viable option in selected severe and critical COVID-19 patients who do not respond to initial steroids. When given along with steroids, a high suspicion of secondary infections should be kept.

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  1. Version published to 10.1101/2021.12.06.21266950v2 on medRxiv
  2. ScreenIT

    SciScore for 10.1101/2021.12.06.21266950: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsConsent: In view of the pure retrospective nature of the study, informed consent was waivered.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power AnalysisStatistical Analysis: Considering a 20% decrease in all cause mortality, as compared to those described in previous studies on critically ill covid patients[12], our sample size came out to be 49 subjects at a power of 90 % & confidence interval of 95 %.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    All statistical analysis was done using SPSS software version 22.
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Our study has some limitations. First, the descriptive nature of our study and absence of a comparator arm allows us to draw no meaningful conclusions from our data about the population and is the major limitation. Moreover, a comparator arm was difficult in the acute setting of pandemic. Secondly, the number of patients observed was very less, thus generalization of the data is not possible. Finally, because of the short follow up period, we were not able to assess the long term safety and adverse effects of tocilizumab.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2021.12.06.21266950v1 on medRxiv