Comments on “Baricitinib versus tocilizumab in mechanically ventilated patients with COVID-19: a nationwide cohort study”

Abstract

Dear Editors,

We read with great interest the article by You et al., which presents a retrospective analysis of South Korean healthcare insurance data comparing the efficacy of baricitinib and tocilizumab in COVID-19 patients receiving mechanical ventilation (MV) [1]. We commend the authors for their valuable contribution to this field, but we believe the following points warrant further consideration in order to enhance the interpretability and clinical applicability of the results.

Firstly, the study spans a relatively long period from October 8, 2020, to October 31, 2022, which may present challenges to data stability and consistency. Given the ongoing nature of the COVID-19 pandemic, many patients may have experienced multiple infections. Studies have demonstrated that recurrent COVID-19 infections not only elevate the overall disease burden in affected individuals but also increase the risk of pulmonary sequelae by 254% in reinfected patients, along with a significantly higher risk of all-cause mortality [2]. Moreover, the multiple variants of the SARS-CoV-2 virus over time could influence its pathogenicity, virulence, and immune escape potential, which in turn may impact treatment efficacy and patient prognosis [3]. Although propensity score matching accounts for some confounding factors, the potential effects of temporal fluctuations in COVID-19 infection and reinfection may not have been fully addressed, which could undermine the reliability of the study's findings.

Furthermore, we note that the study does not clearly specify the baseline treatment regimens, particularly with regard to the use of corticosteroids. According to current clinical guidelines, corticosteroids are commonly used as a standard treatment for COVID-19 patients requiring oxygen support, and antiviral agents and other immunomodulators are also widely utilized [4].. Baricitinib and tocilizumab modulate the immune response by inhibiting specific cytokines, improving clinical outcomes, but the concurrent use of corticosteroids could potentially influence the effectiveness of these drugs. To provide a more comprehensive assessment of the therapeutic effects of baricitinib and tocilizumab, we suggest that the authors include detailed information regarding baseline treatment regimens, particularly concerning corticosteroid and other immunomodulator use. Additionally, subgroup analysis based on corticosteroid use could offer deeper insights into optimizing treatment strategies.

Moreover, the manuscript does not provide specific data on the doses and duration of treatment with baricitinib and tocilizumab. In current clinical practice, the standard regimen for baricitinib is typically 4 mg daily for 14 days or until patient discharge, while the dose of tocilizumab (1 or 2 doses) and the treatment duration may vary depending on the individual. Clarifying drug dosage and treatment duration would help better assess the stability and reproducibility of the treatment effects, strengthening the study's conclusions.

Although the study suggests a beneficial effect of baricitinib in the overall cohort of COVID-19 patients, no significant improvement was observed in the subgroup of patients requiring mechanical ventilation. The RECOVERY trial (2022) showed that baricitinib reduced the 28-day mortality risk by 13% (p = 0.028), but had no significant effect in patients on mechanical ventilation [5]. Additionally, as an oral medication, baricitinib may present absorption issues in patients receiving enteral feeding, and dosage adjustments may be required for those with renal impairment, factors that could limit its efficacy [6]. Therefore, we suggest that the authors further discuss the possible potential influencing factors to enhance the caution and credibility of the study conclusions.

In conclusion, while we greatly appreciate the authors’ work and their contribution to this important field, we believe that addressing the issues outlined above would provide stronger support for a deeper understanding of the role of baricitinib and tocilizumab in the treatment of COVID-19. We look forward to the authors’ response and anticipate that this research will provide valuable insights for clinical practice and future studies.

No datasets were generated or analysed during the current study.

COVID-19:

Coronavirus disease 2019

MV:

Mechanical ventilation

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We would like to express our sincere gratitude to the authors of the article "Baricitinib versus Tocilizumab in Mechanically Ventilated Patients with COVID-19: A Nationwide Cohort Study." We appreciate their comprehensive approach and rigorous data analysis, which have significantly deepened our understanding of the role of Baricitinib and Tocilizumab in the management of COVID-19. We look forward to the authors' further responses, which will undoubtedly provide more insights and inspiration for the ongoing discussions regarding these important therapeutic options.

The Project is supported by the following funds: Science and Technology Department of Shanxi Province Free Exploration Youth Project (No.202303021222314), Shanxi graduate education innovation project (No. 2023SJ137),Shanxi Province Clinical Theranostics Technology Innovation Center for Immunologic and Rheumatic Diseases (No. CXZX-202305), the 2023 COVID-19 Emergency Project of Shanxi Bethune Hospital (No. 2023xg03), the 2023 COVID-19 Emergency Project of Shanxi Health Commission (No. 2023XG002).

Authors and Affiliations

1. Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China

   Rong Li, JuanJuan Wang, Qian Li, QianYue Guo, Jun Kang Zhao & Li-Yun Zhang

2. Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan

   James Cheng-Chung Wei

3. Department of Allergy, Chung Shan Medical University Hospital, Immunology & Rheumatology, Taichung, Taiwan

   James Cheng-Chung Wei

4. Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan

   James Cheng-Chung Wei

5. Shanxi Province Clinical Theranostics Technology Innovation Center for Immunologic and Rheumatic Diseases, Shanxi Province Clinical Research Center for Dermatologic and Immunologic Diseases (Rheumatic diseases), Taiyuan, China

   Rong Li & Li-Yun Zhang

Authors

1. Rong LiView author publications

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2. JuanJuan WangView author publications

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3. Qian LiView author publications

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4. QianYue GuoView author publications

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5. Jun Kang ZhaoView author publications

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6. James Cheng-Chung WeiView author publications

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7. Li-Yun ZhangView author publications

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Contributions

LR mainly wrote the manuscript text, JJW, QL, QYG and JKZ made valuable suggestions, and JCCW and LYZ eventually revised the manuscript. All the authors reviewed the manuscript.

Corresponding authors

Correspondence to James Cheng-Chung Wei or Li-Yun Zhang.

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All authors agree to publication.

Competing interests

The authors declare no competing interests.

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Li, R., Wang, J., Li, Q. et al. Comments on “Baricitinib versus tocilizumab in mechanically ventilated patients with COVID-19: a nationwide cohort study”. Crit Care 28, 428 (2024). https://doi.org/10.1186/s13054-024-05187-5

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• Received: 19 November 2024

• Accepted: 22 November 2024

• Published: 20 December 2024

• DOI: https://doi.org/10.1186/s13054-024-05187-5

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