Combination of Baricitinib plus Remdesivir and Dexamethasone improves time to recovery and mortality among hospitalized patients with severe COVID-19 infection

  1. Victor Perez-Gutierrez
  2. Virali Shah
  3. Afsheen Afzal
  4. Amnah Khalid
  5. Ariane Yangco
  6. Sebastian Ocrospoma
  7. Nail Cemalovic
  8. Anjana Pillai
  9. Moiz kasubhai
  10. Vihren Dimitrov
  11. Vidya Menon

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Abstract

Background

There seems to be a gap in the therapeutic options for severe Covid-19 pneumonia. Though the beneficial effect of combination treatment with baricitnib and remdesivir in accelerating clinical status improvement is described, the impact of the triple therapy with baricitinib + remdesivir/dexamethasone is not known.

Methods

A retrospective observational study comparing the effect of baricitinib plus standard treatment (remdesivir and dexamethasone) with standard therapy in patients requiring ≥ 5 L/min O2 was conducted. The primary outcome was to compared time to recovery in both groups, and the secondary outcomes was to determine mortality rate at discharge.

Results

Of 457 patients hospitalized during the study period, 51 patients received standard treatment while 88 patients received baricitinib plus standard treatment. In baricitinib group, the rate ratio of recovery was 1.28 (95%CI 0.84-1.94, p=0.24) with a reduction in median time to recovery of 3 days compared to standard treatment group. Subgroup analysis based on Ordinal Scale showed reduction in median time to recovery by 4 and 2 days with rate ratio of recovery of 2.95 (1.03-8.42, p =0.04) and 1.80 (1.09-2.98, p=0.02) in Ordinal Scale 5 and 6 respectively. No benefit was found in the Ordinal Scale 7 subgroup. An overall decrease in rate (15.9% vs 31.4% p=0.03) a likelihood (OR 0.41, 95%CI 0.18-0.94, p=0.03) of mortality was observed in the baricitinib group. Bacteremia and thrombosis were noted in the Baricitinib group, but comparable with the Standard of care group.

Conclusion

Baricitinib with standard therapy reduced time to recovery and offer mortality benefit in patients with severe COVID-19 pneumonia.”

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  1. ScreenIT

    SciScore for 10.1101/2022.04.04.22273425: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Study design and patient population: This a case-control retrospective study in a New York City Health + Hospital acute care facility in the South Bronx, approved by the Institutional Review Board [IRB # 21-007].
    Sex as a biological variableThe median age was 63 years with 56.1% being male and predominant Latinx (74.1%) followed by African-Americans (18.0%).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Statistical analysis was conducted using IBM SPSS Statistics 27 (IBM Corp., Armonk, NY, USA) software. Results: Of the 584 patients hospitalized with COVID-19 pneumonia from July 1, 2020, to Feb 20, 2021, 175/584 (29.9%) patients requiring 5 or more liters of supplemental O2 were screened for the study.
    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 had several limitations; firstly, this retrospective observational study included two groups of hospitalized COVID-19 pneumonia patients from two different timeframes (July-Dec 2020 and Jan-Feb 20, 2021). Though these groups had a similar distribution in demographic, baseline characteristics, and burden of the disease, we accept that there were confounders including “variants of concern” and mortality differences due to comparatively lesser burden of disease in the July-Dec timeframe. The study is also limited by sample size and generalizability. There was no standard length of therapy for the baricitinib-treated group and ranged from 3 to 10 days. The decision to stop baricitinib was at the discretion of the treating physician based on the patient’s clinical improvement. Thirdly we had two patients still hospitalized on mechanical ventilation, without a clear outcome, when the data was analyzed. Fourthly, the inherent limitations of retrospective studies, especially lack randomization, cannot be ignored, though we believe our encouraging results contribute to the therapeutic options for hospitalized severe COVID-19 patients till further robust data/evidence is available. Lastly, the lack of benefit in patients requiring mechanical ventilation could be due to the smaller sample size.

    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

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  2. Version published to 10.1101/2022.04.04.22273425v1 on medRxiv