Ruxolitinib versus dexamethasone in hospitalized adults with COVID-19: multicenter matched cohort study

  1. O. V. Stanevich
  2. D. S. Fomina
  3. I. G. Bakulin
  4. S. I. Galeev
  5. E. A. Bakin
  6. V. A. Belash
  7. A. N. Kulikov
  8. A. A. Lebedeva
  9. D. A. Lioznov
  10. Yu. S. Polushin
  11. I. V. Shlyk
  12. E. A. Vorobyev
  13. S. V. Vorobyeva
  14. T. V. Surovceva
  15. N. V. Bakulina
  16. M. A. Lysenko
  17. I. S. Moiseev

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Abstract

Background

Several anti-cytokine therapies were tested in the randomized trials in hospitalized patients with severe acute respiratory syndrome coronavirus 2 infection (COVID-19). Previously, dexamethasone demonstrated a reduction of case-fatality rate in hospitalized patients with respiratory failure. In this matched control study we compared dexamethasone to a Janus kinase inhibitor, ruxolitinib.

Methods

The matched cohort study included 146 hospitalized patients with COVID-19 and oxygen support requirement. The control group was selected 1:1 from 1355 dexamethasone-treated patients and was matched by main clinical and laboratory parameters predicting survival. Recruitment period was April 7, 2020 through September 9, 2020.

Results

Ruxolitinib treatment in the general cohort of patients was associated with case-fatality rate similar to dexamethasone treatment: 9.6% (95% CI [4.6–14.6%]) vs 13.0% (95% CI [7.5–18.5%]) respectively ( p  = 0.35, OR = 0.71, 95% CI [0.31–1.57]). Median time to discharge without oxygen support requirement was also not different between these groups: 13 vs. 11 days ( p  = 0.13). Subgroup analysis without adjustment for multiple comparisons demonstrated a reduced case-fatality rate in ruxolitnib-treated patients with a high fever (≥ 38.5 °C) (OR 0.33, 95% CI [0.11–1.00]). Except higher incidence of grade 1 thrombocytopenia (37% vs 23%, p  = 0.042), ruxolitinib therapy was associated with a better safety profile due to a reduced rate of severe cardiovascular adverse events (6.8% vs 15%, p  = 0.025). For 32 patients from ruxolitinib group (21.9%) with ongoing progression of respiratory failure after 72 h of treatment, additional anti-cytokine therapy was prescribed (8–16 mg dexamethasone).

Conclusions

Ruxolitinib may be an alternative initial anti-cytokine therapy with comparable effectiveness in patients with potential risks of steroid administration. Patients with a high fever (≥ 38.5 °C) at admission may potentially benefit from ruxolitinib administration.

Trial registration The Ruxolitinib Managed Access Program (MAP) for Patients Diagnosed With Severe/Very Severe COVID-19 Illness NCT04337359, CINC424A2001M, registered April, 7, 2020. First participant was recruited after registration date

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  1. Version published to 10.1186/s12879-021-06982-z
  2. Version published to 10.21203/rs.3.rs-605939/v1 on Research Square
  3. ScreenIT

    SciScore for 10.1101/2021.04.20.21255662: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Local ethical committees approved the participation of patients in the Managed Access Program and all patients signed informed consent for the treatment.
    Consent: Local ethical committees approved the participation of patients in the Managed Access Program and all patients signed informed consent for the treatment.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Local ethical committees approved the participation of patients in the Managed Access Program and all patients signed informed consent for the treatment.
    Managed Access Program
    suggested: None

    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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04337359No longer availableRuxolitinib Managed Access Program (MAP) for Patients Diagno…

    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.

    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.

  4. Version published to 10.1101/2021.04.20.21255662v1 on medRxiv