评论巴利昔尼与托珠单抗在COVID-19机械通气患者中的应用:一项全国性队列研究

IF 8.8 1区 医学 Q1 CRITICAL CARE MEDICINE
James Cheng Chung Wei, Poi Kuo, Po-Cheng Shih
{"title":"评论巴利昔尼与托珠单抗在COVID-19机械通气患者中的应用:一项全国性队列研究","authors":"James Cheng Chung Wei, Poi Kuo, Po-Cheng Shih","doi":"10.1186/s13054-024-05116-6","DOIUrl":null,"url":null,"abstract":"<p>We read with great interest the article by You et al., which provides valuable insights into the comparative efficacy of baricitinib and tocilizumab in mechanically ventilated COVID-19 patients [1]. While the study’s findings are important, especially regarding the lower 30-day mortality in the baricitinib group, we believe that the issue of confounding by indication was not sufficiently addressed and may have significantly influenced the results.</p><p>Confounding by indication occurs when treatment assignment is influenced by disease severity, leading to a bias in outcome comparison between treatment groups. In this study, patients in the tocilizumab group appeared to be more severely ill at baseline compared to those in the baricitinib group. Although the authors employed propensity score matching (PSM) to balance baseline characteristics, the data suggest that the tocilizumab group had a higher severity of illness, which could explain some of the observed differences in mortality. Notably, patients in the tocilizumab group had longer durations of mechanical ventilation prior to drug administration, higher use of extracorporeal membrane oxygenation (ECMO), and more severe comorbidities, as detailed in the supplementary tables. These factors strongly suggest that tocilizumab was more likely administered to patients in critical condition, potentially skewing the mortality comparison in favor of baricitinib.</p><p>Furthermore, while PSM is effective at balancing observable variables, it may not fully account for unmeasured or residual confounders, such as the timing of drug administration relative to disease progression or the specific clinical criteria that influenced treatment choices. Baricitinib was administered for a median of 8 days, while tocilizumab was often given as a single dose. This difference in treatment duration and pharmacodynamics could have further impacted the results. Baricitinib, with its broader anti-inflammatory effects and prolonged administration, may have provided a more sustained reduction in inflammation, whereas the single-dose nature of tocilizumab could have limited its efficacy in severely ill patients.</p><p>Additionally, the study does not provide sufficient detail regarding the criteria used to determine whether a patient received baricitinib or tocilizumab beyond the similar indications in general consideration [2]. Without understanding the clinical decision-making process, it is difficult to evaluate the extent to which confounding by indication may have influenced the results. If tocilizumab was preferentially administered to patients with more rapidly progressing or refractory disease, the higher mortality rate in this group might reflect underlying disease severity rather than a difference in drug efficacy [3]. </p><p>It may be beneficial to consider a subgroup analysis excluding patients requiring total parenteral nutrition (TPN), as those unable to tolerate enteral nutrition typically represent a more critically ill population with poorer prognostic indicators, such as higher Sequential Organ Failure Assessment (SOFA) scores [4]. These patients are more likely to receive intravenous therapies, including tocilizumab, which is administered as an injection. This could introduce a potential confounder, as the preference for tocilizumab in this critically ill subgroup might reflect the inability to administer oral medications like baricitinib, rather than a direct reflection of the drug’s relative efficacy. Consequently, these factors could disproportionately affect mortality rates in the tocilizumab group, further complicating direct efficacy comparisons.</p><p>In light of these concerns, we suggest that future studies consider using SOFA or APACHE II scores in PSM to better control for baseline severity differences. If SOFA or APACHE II data are unavailable, matching based on laboratory data associated with SOFA or APACHE II scores at the time of ICU admission or intubation could serve as a proxy for disease severity [5,6,7]. Incorporating these variables may help mitigate confounding and strengthen the conclusions. Additionally, more detailed time-dependent analyses, such as the duration of mechanical ventilation or timing of drug administration, would clarify the true effects of these therapies in critically ill patients.</p><p>Ultimately, randomized controlled trials remain the gold standard to address these concerns, but in the interim, the use of more nuanced statistical matching techniques may help refine comparisons between baricitinib and tocilizumab in this population.</p><p>No datasets were generated or analysed during the current study.</p><ol data-track-component=\"outbound reference\" data-track-context=\"references section\"><li data-counter=\"1.\"><p>You S-H, Baek MS, Kim TW, Jung S-Y, Kim W-Y. Baricitinib versus tocilizumab in mechanically ventilated patients with COVID–19: a nationwide cohort study. Crit Care. 2024;28(1):282.</p><p>Article PubMed PubMed Central Google Scholar </p></li><li data-counter=\"2.\"><p>Liu LT, Tsai JJ. Unveiling COVID–19 treatment strategies for immunocompromised individuals: terapeutic innovations and latest findings. Hoboken: Wiley; 2024. p. e14900.</p><p>Google Scholar </p></li><li data-counter=\"3.\"><p>Trøseid M, Arribas JR, Assoumou L, Holten AR, Poissy J, Terzić V, et al. Efficacy and safety of baricitinib in hospitalized adults with severe or critical COVID–19 (Bari-SolidAct): a randomised, double-blind, placebo-controlled phase 3 trial. Crit Care. 2023;27(1):9.</p><p>Article PubMed PubMed Central Google Scholar </p></li><li data-counter=\"4.\"><p>Lopez-Delgado JC, Servia-Goixart L, Grau-Carmona T, Bordeje-Laguna L, Portugal-Rodriguez E, Lorencio-Cardenas C, et al. Factors associated with the need of parenteral nutrition in critically ill patients after the initiation of enteral nutrition therapy. Front Nutr. 2023;10:1250305.</p><p>Article PubMed PubMed Central Google Scholar </p></li><li data-counter=\"5.\"><p>Vicka V, Januskeviciute E, Miskinyte S, Ringaitiene D, Serpytis M, Klimasauskas A, et al. Comparison of mortality risk evaluation tools efficacy in critically ill COVID–19 patients. BMC Infect Dis. 2021;21:1–7.</p><p>Article Google Scholar </p></li><li data-counter=\"6.\"><p>Beigmohammadi MT, Amoozadeh L, Rezaei Motlagh F, Rahimi M, Maghsoudloo M, Jafarnejad B, et al. Mortality predictive value of APACHE II and SOFA scores in COVID–19 patients in the intensive care unit. Can Respir J. 2022;2022(1):5129314.</p><p>PubMed PubMed Central Google Scholar </p></li><li data-counter=\"7.\"><p>Roddy J, Wells D, Schenck K, Santosh S, Santosh S. Tocilizumab versus baricitinib in patients hospitalized with COVID–19 pneumonia and hypoxemia: a multicenter retrospective cohort study. Crit Care Explor. 2022;4(5):e0702.</p><p>Article PubMed PubMed Central Google Scholar </p></li></ol><p>Download references<svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></p><p>No funding involved</p><h3>Authors and Affiliations</h3><ol><li><p>Department of Allergy, Immunology &amp; Rheumatology, Chung Shan Medical University Hospital, Section 1, Jianguo N Rd, Taichung, 402, Taiwan</p><p>James Cheng Chung Wei</p></li><li><p>Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan</p><p>James Cheng Chung Wei &amp; Po-Cheng Shih</p></li><li><p>Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan</p><p>James Cheng Chung Wei</p></li><li><p>Chung Shan Medical University Hospital, Taichung, Taiwan</p><p>Poi Kuo</p></li><li><p>Department of Allergy, Immunology &amp; Rheumatology, Changhua Christian Hospital, Changhua, Taiwan</p><p>Po-Cheng Shih</p></li><li><p>Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, 030032, China</p><p>James Cheng Chung Wei</p></li><li><p>Institute of Medicine/Department of Nursing, Chung Shan Medical University, Taichung, Taiwan</p><p>James Cheng Chung Wei</p></li></ol><span>Authors</span><ol><li><span>James Cheng Chung Wei</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Poi Kuo</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Po-Cheng Shih</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li></ol><h3>Contributions</h3><p>All authors wrote and revised the manuscript.</p><h3>Corresponding author</h3><p>Correspondence to Po-Cheng Shih.</p><h3>Conflict of interest</h3>\n<p>The authors declare no competing interests.</p><h3>Publisher’s note</h3><p>Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.</p><p><b>Open Access</b> This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.</p>\n<p>Reprints and permissions</p><img alt=\"Check for updates. 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0-.92-.08-1.33-.25-.41-.16-.77-.4-1.08-.7-.3-.31-.54-.69-.72-1.13-.17-.44-.26-.95-.26-1.52zm4.61-.62c0-.55-.11-.98-.34-1.28-.23-.31-.58-.47-1.06-.47-.41 0-.77.15-1.08.45-.31.29-.5.73-.57 1.3zm3.01 2.23c.31.24.61.43.92.57.3.13.63.2.98.2.38 0 .65-.08.83-.23s.27-.35.27-.6c0-.14-.05-.26-.13-.37-.08-.1-.2-.2-.34-.28-.14-.09-.29-.16-.47-.23l-.53-.22c-.23-.09-.46-.18-.69-.3-.23-.11-.44-.24-.62-.4s-.33-.35-.45-.55c-.12-.21-.18-.46-.18-.75 0-.61.23-1.1.68-1.49.44-.38 1.06-.57 1.83-.57.48 0 .91.08 1.29.25s.71.36.99.57l-.74.98c-.24-.17-.49-.32-.73-.42-.25-.11-.51-.16-.78-.16-.35 0-.6.07-.76.21-.17.15-.25.33-.25.54 0 .14.04.26.12.36s.18.18.31.26c.14.07.29.14.46.21l.54.19c.23.09.47.18.7.29s.44.24.64.4c.19.16.34.35.46.58.11.23.17.5.17.82 0 .3-.06.58-.17.83-.12.26-.29.48-.51.68-.23.19-.51.34-.84.45-.34.11-.72.17-1.15.17-.48 0-.95-.09-1.41-.27-.46-.19-.86-.41-1.2-.68z" fill="#535353"/></g></svg>\" width=\"57\"/><h3>Cite this article</h3><p>Wei, J.C.C., Kuo, P. &amp; Shih, PC. Commenting on baricitinib versus tocilizumab in mechanically ventilated patients with COVID-19: a nationwide cohort study. <i>Crit Care</i> <b>28</b>, 357 (2024). https://doi.org/10.1186/s13054-024-05116-6</p><p>Download citation<svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></p><ul data-test=\"publication-history\"><li><p>Received<span>: </span><span><time datetime=\"2024-09-26\">26 September 2024</time></span></p></li><li><p>Accepted<span>: </span><span><time datetime=\"2024-09-30\">30 September 2024</time></span></p></li><li><p>Published<span>: </span><span><time datetime=\"2024-11-05\">05 November 2024</time></span></p></li><li><p>DOI</abbr><span>: </span><span>https://doi.org/10.1186/s13054-024-05116-6</span></p></li></ul><h3>Share this article</h3><p>Anyone you share the following link with will be able to read this content:</p><button data-track=\"click\" data-track-action=\"get shareable link\" data-track-external=\"\" data-track-label=\"button\" type=\"button\">Get shareable link</button><p>Sorry, a shareable link is not currently available for this article.</p><p data-track=\"click\" data-track-action=\"select share url\" data-track-label=\"button\"></p><button data-track=\"click\" data-track-action=\"copy share url\" data-track-external=\"\" data-track-label=\"button\" type=\"button\">Copy to clipboard</button><p> Provided by the Springer Nature SharedIt content-sharing initiative </p>","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":null,"pages":null},"PeriodicalIF":8.8000,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Commenting on baricitinib versus tocilizumab in mechanically ventilated patients with COVID-19: a nationwide cohort study\",\"authors\":\"James Cheng Chung Wei, Poi Kuo, Po-Cheng Shih\",\"doi\":\"10.1186/s13054-024-05116-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>We read with great interest the article by You et al., which provides valuable insights into the comparative efficacy of baricitinib and tocilizumab in mechanically ventilated COVID-19 patients [1]. While the study’s findings are important, especially regarding the lower 30-day mortality in the baricitinib group, we believe that the issue of confounding by indication was not sufficiently addressed and may have significantly influenced the results.</p><p>Confounding by indication occurs when treatment assignment is influenced by disease severity, leading to a bias in outcome comparison between treatment groups. In this study, patients in the tocilizumab group appeared to be more severely ill at baseline compared to those in the baricitinib group. Although the authors employed propensity score matching (PSM) to balance baseline characteristics, the data suggest that the tocilizumab group had a higher severity of illness, which could explain some of the observed differences in mortality. Notably, patients in the tocilizumab group had longer durations of mechanical ventilation prior to drug administration, higher use of extracorporeal membrane oxygenation (ECMO), and more severe comorbidities, as detailed in the supplementary tables. These factors strongly suggest that tocilizumab was more likely administered to patients in critical condition, potentially skewing the mortality comparison in favor of baricitinib.</p><p>Furthermore, while PSM is effective at balancing observable variables, it may not fully account for unmeasured or residual confounders, such as the timing of drug administration relative to disease progression or the specific clinical criteria that influenced treatment choices. Baricitinib was administered for a median of 8 days, while tocilizumab was often given as a single dose. This difference in treatment duration and pharmacodynamics could have further impacted the results. Baricitinib, with its broader anti-inflammatory effects and prolonged administration, may have provided a more sustained reduction in inflammation, whereas the single-dose nature of tocilizumab could have limited its efficacy in severely ill patients.</p><p>Additionally, the study does not provide sufficient detail regarding the criteria used to determine whether a patient received baricitinib or tocilizumab beyond the similar indications in general consideration [2]. Without understanding the clinical decision-making process, it is difficult to evaluate the extent to which confounding by indication may have influenced the results. If tocilizumab was preferentially administered to patients with more rapidly progressing or refractory disease, the higher mortality rate in this group might reflect underlying disease severity rather than a difference in drug efficacy [3]. </p><p>It may be beneficial to consider a subgroup analysis excluding patients requiring total parenteral nutrition (TPN), as those unable to tolerate enteral nutrition typically represent a more critically ill population with poorer prognostic indicators, such as higher Sequential Organ Failure Assessment (SOFA) scores [4]. These patients are more likely to receive intravenous therapies, including tocilizumab, which is administered as an injection. This could introduce a potential confounder, as the preference for tocilizumab in this critically ill subgroup might reflect the inability to administer oral medications like baricitinib, rather than a direct reflection of the drug’s relative efficacy. Consequently, these factors could disproportionately affect mortality rates in the tocilizumab group, further complicating direct efficacy comparisons.</p><p>In light of these concerns, we suggest that future studies consider using SOFA or APACHE II scores in PSM to better control for baseline severity differences. If SOFA or APACHE II data are unavailable, matching based on laboratory data associated with SOFA or APACHE II scores at the time of ICU admission or intubation could serve as a proxy for disease severity [5,6,7]. Incorporating these variables may help mitigate confounding and strengthen the conclusions. Additionally, more detailed time-dependent analyses, such as the duration of mechanical ventilation or timing of drug administration, would clarify the true effects of these therapies in critically ill patients.</p><p>Ultimately, randomized controlled trials remain the gold standard to address these concerns, but in the interim, the use of more nuanced statistical matching techniques may help refine comparisons between baricitinib and tocilizumab in this population.</p><p>No datasets were generated or analysed during the current study.</p><ol data-track-component=\\\"outbound reference\\\" data-track-context=\\\"references section\\\"><li data-counter=\\\"1.\\\"><p>You S-H, Baek MS, Kim TW, Jung S-Y, Kim W-Y. Baricitinib versus tocilizumab in mechanically ventilated patients with COVID–19: a nationwide cohort study. Crit Care. 2024;28(1):282.</p><p>Article PubMed PubMed Central Google Scholar </p></li><li data-counter=\\\"2.\\\"><p>Liu LT, Tsai JJ. Unveiling COVID–19 treatment strategies for immunocompromised individuals: terapeutic innovations and latest findings. Hoboken: Wiley; 2024. p. e14900.</p><p>Google Scholar </p></li><li data-counter=\\\"3.\\\"><p>Trøseid M, Arribas JR, Assoumou L, Holten AR, Poissy J, Terzić V, et al. Efficacy and safety of baricitinib in hospitalized adults with severe or critical COVID–19 (Bari-SolidAct): a randomised, double-blind, placebo-controlled phase 3 trial. Crit Care. 2023;27(1):9.</p><p>Article PubMed PubMed Central Google Scholar </p></li><li data-counter=\\\"4.\\\"><p>Lopez-Delgado JC, Servia-Goixart L, Grau-Carmona T, Bordeje-Laguna L, Portugal-Rodriguez E, Lorencio-Cardenas C, et al. Factors associated with the need of parenteral nutrition in critically ill patients after the initiation of enteral nutrition therapy. Front Nutr. 2023;10:1250305.</p><p>Article PubMed PubMed Central Google Scholar </p></li><li data-counter=\\\"5.\\\"><p>Vicka V, Januskeviciute E, Miskinyte S, Ringaitiene D, Serpytis M, Klimasauskas A, et al. Comparison of mortality risk evaluation tools efficacy in critically ill COVID–19 patients. BMC Infect Dis. 2021;21:1–7.</p><p>Article Google Scholar </p></li><li data-counter=\\\"6.\\\"><p>Beigmohammadi MT, Amoozadeh L, Rezaei Motlagh F, Rahimi M, Maghsoudloo M, Jafarnejad B, et al. Mortality predictive value of APACHE II and SOFA scores in COVID–19 patients in the intensive care unit. Can Respir J. 2022;2022(1):5129314.</p><p>PubMed PubMed Central Google Scholar </p></li><li data-counter=\\\"7.\\\"><p>Roddy J, Wells D, Schenck K, Santosh S, Santosh S. Tocilizumab versus baricitinib in patients hospitalized with COVID–19 pneumonia and hypoxemia: a multicenter retrospective cohort study. Crit Care Explor. 2022;4(5):e0702.</p><p>Article PubMed PubMed Central Google Scholar </p></li></ol><p>Download references<svg aria-hidden=\\\"true\\\" focusable=\\\"false\\\" height=\\\"16\\\" role=\\\"img\\\" width=\\\"16\\\"><use xlink:href=\\\"#icon-eds-i-download-medium\\\" xmlns:xlink=\\\"http://www.w3.org/1999/xlink\\\"></use></svg></p><p>No funding involved</p><h3>Authors and Affiliations</h3><ol><li><p>Department of Allergy, Immunology &amp; Rheumatology, Chung Shan Medical University Hospital, Section 1, Jianguo N Rd, Taichung, 402, Taiwan</p><p>James Cheng Chung Wei</p></li><li><p>Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan</p><p>James Cheng Chung Wei &amp; Po-Cheng Shih</p></li><li><p>Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan</p><p>James Cheng Chung Wei</p></li><li><p>Chung Shan Medical University Hospital, Taichung, Taiwan</p><p>Poi Kuo</p></li><li><p>Department of Allergy, Immunology &amp; Rheumatology, Changhua Christian Hospital, Changhua, Taiwan</p><p>Po-Cheng Shih</p></li><li><p>Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, 030032, China</p><p>James Cheng Chung Wei</p></li><li><p>Institute of Medicine/Department of Nursing, Chung Shan Medical University, Taichung, Taiwan</p><p>James Cheng Chung Wei</p></li></ol><span>Authors</span><ol><li><span>James Cheng Chung Wei</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Poi Kuo</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Po-Cheng Shih</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li></ol><h3>Contributions</h3><p>All authors wrote and revised the manuscript.</p><h3>Corresponding author</h3><p>Correspondence to Po-Cheng Shih.</p><h3>Conflict of interest</h3>\\n<p>The authors declare no competing interests.</p><h3>Publisher’s note</h3><p>Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.</p><p><b>Open Access</b> This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.</p>\\n<p>Reprints and permissions</p><img alt=\\\"Check for updates. 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Commenting on baricitinib versus tocilizumab in mechanically ventilated patients with COVID-19: a nationwide cohort study. <i>Crit Care</i> <b>28</b>, 357 (2024). https://doi.org/10.1186/s13054-024-05116-6</p><p>Download citation<svg aria-hidden=\\\"true\\\" focusable=\\\"false\\\" height=\\\"16\\\" role=\\\"img\\\" width=\\\"16\\\"><use xlink:href=\\\"#icon-eds-i-download-medium\\\" xmlns:xlink=\\\"http://www.w3.org/1999/xlink\\\"></use></svg></p><ul data-test=\\\"publication-history\\\"><li><p>Received<span>: </span><span><time datetime=\\\"2024-09-26\\\">26 September 2024</time></span></p></li><li><p>Accepted<span>: </span><span><time datetime=\\\"2024-09-30\\\">30 September 2024</time></span></p></li><li><p>Published<span>: </span><span><time datetime=\\\"2024-11-05\\\">05 November 2024</time></span></p></li><li><p>DOI</abbr><span>: </span><span>https://doi.org/10.1186/s13054-024-05116-6</span></p></li></ul><h3>Share this article</h3><p>Anyone you share the following link with will be able to read this content:</p><button data-track=\\\"click\\\" data-track-action=\\\"get shareable link\\\" data-track-external=\\\"\\\" data-track-label=\\\"button\\\" type=\\\"button\\\">Get shareable link</button><p>Sorry, a shareable link is not currently available for this article.</p><p data-track=\\\"click\\\" data-track-action=\\\"select share url\\\" data-track-label=\\\"button\\\"></p><button data-track=\\\"click\\\" data-track-action=\\\"copy share url\\\" data-track-external=\\\"\\\" data-track-label=\\\"button\\\" type=\\\"button\\\">Copy to clipboard</button><p> Provided by the Springer Nature SharedIt content-sharing initiative </p>\",\"PeriodicalId\":10811,\"journal\":{\"name\":\"Critical Care\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":8.8000,\"publicationDate\":\"2024-11-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Critical Care\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s13054-024-05116-6\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CRITICAL CARE MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Critical Care","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13054-024-05116-6","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CRITICAL CARE MEDICINE","Score":null,"Total":0}
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我们饶有兴趣地阅读了You等人的文章,该文对巴利昔尼和妥昔单抗在机械通气的COVID-19患者中的疗效比较提供了有价值的见解[1]。虽然该研究的结果很重要,尤其是巴利替尼组的 30 天死亡率较低,但我们认为适应症混杂问题没有得到充分解决,可能会对结果产生重大影响。在这项研究中,与巴利昔尼组相比,托西珠单抗组患者的基线病情似乎更严重。虽然作者采用了倾向评分匹配(PSM)来平衡基线特征,但数据表明托西珠单抗组患者的病情严重程度更高,这可能是观察到的死亡率差异的部分原因。值得注意的是,托西珠单抗组患者在用药前的机械通气时间更长,体外膜肺氧合(ECMO)的使用率更高,合并症更严重,详见补充表格。这些因素有力地表明,托西珠单抗更有可能用于病情危重的患者,从而有可能使死亡率比较向巴利替尼倾斜。此外,虽然PSM能有效平衡可观察变量,但它可能无法完全考虑未测量或残留的混杂因素,如相对于疾病进展的给药时间或影响治疗选择的特定临床标准。巴利替尼的中位给药时间为 8 天,而托珠单抗通常为单次给药。这种治疗时间和药效学上的差异可能会进一步影响治疗结果。巴利昔尼具有更广泛的抗炎作用,且用药时间较长,可能会更持久地减轻炎症,而托珠单抗的单剂量性质可能会限制其在重症患者中的疗效。此外,除了一般考虑的类似适应症外,该研究没有提供足够详细的资料说明确定患者接受巴利昔尼还是托珠单抗的标准[2]。在不了解临床决策过程的情况下,很难评估适应症对结果的影响程度。如果托珠单抗优先用于病情进展较快或难治性疾病患者,那么该组患者较高的死亡率可能反映了潜在疾病的严重程度,而不是药物疗效的差异[3]。考虑将需要全肠外营养(TPN)的患者排除在外进行亚组分析可能是有益的,因为不能耐受肠内营养的患者通常病情较重,预后指标较差,如序贯器官衰竭评估(SOFA)评分较高[4]。这些患者更有可能接受静脉注射疗法,包括以注射方式给药的托珠单抗。这可能会带来一个潜在的混杂因素,因为在这一重症亚组中偏好使用托西珠单抗可能反映了无法使用巴利替尼等口服药物,而不是直接反映了药物的相对疗效。有鉴于此,我们建议未来的研究考虑在 PSM 中使用 SOFA 或 APACHE II 评分,以更好地控制基线严重程度差异。如果无法获得 SOFA 或 APACHE II 数据,则可根据 ICU 入院或插管时与 SOFA 或 APACHE II 评分相关的实验室数据进行匹配,作为疾病严重程度的替代指标[5,6,7]。纳入这些变量可能有助于减少混杂因素并强化结论。此外,更详细的时间依赖性分析,如机械通气持续时间或给药时间,将明确这些疗法在重症患者中的真正效果。最终,随机对照试验仍是解决这些问题的黄金标准,但在此期间,使用更细致的统计匹配技术可能有助于完善巴利昔尼与托珠单抗在这一人群中的比较。You S-H, Baek MS, Kim TW, Jung S-Y, Kim W-Y. Baricitinib versus tocilizumab in mechanically ventilated patients with COVID-19: a nationwide cohort study.Crit Care.2024;28(1):282.Article PubMed PubMed Central Google Scholar Liu LT, Tsai JJ.揭示免疫功能低下者的 COVID-19 治疗策略:治疗创新与最新发现。 Hoboken:Google Scholar Trøseid M, Arribas JR, Assoumou L, Holten AR, Poissy J, Terzić V, et al. Baricitinib in hospitalized adults with severe or critical COVID-19 (Bari-SolidAct): a randomised, double-blind, placebo controlled phase 3 trial.Crit Care.2023;27(1):9.Article PubMed PubMed Central Google Scholar Lopez-Delgado JC, Servia-Goixart L, Grau-Carmona T, Bordeje-Laguna L, Portugal-Rodriguez E, Lorencio-Cardenas C, et al.Front Nutr. 2023;10:1250305.Article PubMed PubMed Central Google Scholar Vicka V, Januskeviciute E, Miskinyte S, Ringaitiene D, Serpytis M, Klimasauskas A, et al.COVID-19重症患者死亡风险评估工具功效比较。BMC Infect Dis.2021;21:1-7.Article Google Scholar Beigmohammadi MT, Amoozadeh L, Rezaei Motlagh F, Rahimi M, Maghsoudloo M, Jafarnejad B, et al. Mortality predictive value of APACHE II and SOFA scores in COVID-19 patients in the intensive care unit.Can Respir J. 2022;2022(1):5129314.PubMed PubMed Central Google Scholar Roddy J, Wells D, Schenck K, Santosh S, Santosh S. Tocilizumab versus baricitinib in patients in hospitalized with COVID-19 pneumonia and hypoxemia: a multicenter retrospective cohort study.Crit Care Explor.2022;4(5):e0702.Article PubMed PubMed Central Google Scholar Download referencesNo funding involved作者及工作单位中山医学大学附属医院过敏免疫风湿科,台中市建国北路一段1号,402,台湾中山医学大学医学研究所,台中市中山医学大学医学研究所,台中市中山医学大学医学研究所,台中市Po-Cheng Shih 台灣台中,中國醫藥大學中西醫結合研究所 James Cheng Chung Wei 台灣台中,中山醫學大學附設醫院 Poi Kuo 台灣台中,彰化縣立中山醫學大學附設醫院 Allergy, Immunology &amp;山西省医学科学院山西白求恩医院,山西医科大学第三医院,山西同济医院,太原,030032,中国James Cheng Chung Wei台中,中山医科大学医学研究所/护理学系、台湾James Cheng Chung Wei作者简介James Cheng Chung Wei查看作者发表的论文您也可以在PubMed Google Scholar中搜索该作者Poi Kuo查看作者发表的论文您也可以在PubMed Google Scholar中搜索该作者Po-Cheng Shih查看作者发表的论文您也可以在PubMed Google Scholar中搜索该作者Contributions所有作者撰写并修改了手稿。通讯作者Po-Cheng Shih.利益冲突作者声明无利益冲突.出版者注释Springer Nature对出版地图中的管辖权主张和机构隶属关系保持中立.开放获取本文采用知识共享署名-非商业性-禁止衍生 4.0 国际许可协议,该协议允许以任何媒介或格式进行非商业性使用、共享、分发和复制,只要您适当注明原作者和来源,提供知识共享许可协议的链接,并说明您是否修改了许可材料。根据本许可协议,您无权分享源自本文或本文部分内容的改编材料。本文中的图片或其他第三方材料均包含在文章的知识共享许可协议中,除非在材料的信用栏中另有说明。如果材料未包含在文章的知识共享许可协议中,且您打算使用的材料不符合法律规定或超出了许可使用范围,则您需要直接获得版权所有者的许可。要查看该许可的副本,请访问 http://creativecommons.org/licenses/by-nc-nd/4.0/.Reprints and permissionsCite this articleWei, J.C.C., Kuo, P. &amp; Shih, PC.评论COVID-19机械通气患者中的巴利昔尼与托珠单抗:一项全国性队列研究。https://doi.org/10.1186/s13054-024-05116-6Download citationReceived:2024年9月26日接受:30 September 2024Published: 05 November 2024DOI: https://doi.org/10.1186/s13054-024-05116-6Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Commenting on baricitinib versus tocilizumab in mechanically ventilated patients with COVID-19: a nationwide cohort study

We read with great interest the article by You et al., which provides valuable insights into the comparative efficacy of baricitinib and tocilizumab in mechanically ventilated COVID-19 patients [1]. While the study’s findings are important, especially regarding the lower 30-day mortality in the baricitinib group, we believe that the issue of confounding by indication was not sufficiently addressed and may have significantly influenced the results.

Confounding by indication occurs when treatment assignment is influenced by disease severity, leading to a bias in outcome comparison between treatment groups. In this study, patients in the tocilizumab group appeared to be more severely ill at baseline compared to those in the baricitinib group. Although the authors employed propensity score matching (PSM) to balance baseline characteristics, the data suggest that the tocilizumab group had a higher severity of illness, which could explain some of the observed differences in mortality. Notably, patients in the tocilizumab group had longer durations of mechanical ventilation prior to drug administration, higher use of extracorporeal membrane oxygenation (ECMO), and more severe comorbidities, as detailed in the supplementary tables. These factors strongly suggest that tocilizumab was more likely administered to patients in critical condition, potentially skewing the mortality comparison in favor of baricitinib.

Furthermore, while PSM is effective at balancing observable variables, it may not fully account for unmeasured or residual confounders, such as the timing of drug administration relative to disease progression or the specific clinical criteria that influenced treatment choices. Baricitinib was administered for a median of 8 days, while tocilizumab was often given as a single dose. This difference in treatment duration and pharmacodynamics could have further impacted the results. Baricitinib, with its broader anti-inflammatory effects and prolonged administration, may have provided a more sustained reduction in inflammation, whereas the single-dose nature of tocilizumab could have limited its efficacy in severely ill patients.

Additionally, the study does not provide sufficient detail regarding the criteria used to determine whether a patient received baricitinib or tocilizumab beyond the similar indications in general consideration [2]. Without understanding the clinical decision-making process, it is difficult to evaluate the extent to which confounding by indication may have influenced the results. If tocilizumab was preferentially administered to patients with more rapidly progressing or refractory disease, the higher mortality rate in this group might reflect underlying disease severity rather than a difference in drug efficacy [3].

It may be beneficial to consider a subgroup analysis excluding patients requiring total parenteral nutrition (TPN), as those unable to tolerate enteral nutrition typically represent a more critically ill population with poorer prognostic indicators, such as higher Sequential Organ Failure Assessment (SOFA) scores [4]. These patients are more likely to receive intravenous therapies, including tocilizumab, which is administered as an injection. This could introduce a potential confounder, as the preference for tocilizumab in this critically ill subgroup might reflect the inability to administer oral medications like baricitinib, rather than a direct reflection of the drug’s relative efficacy. Consequently, these factors could disproportionately affect mortality rates in the tocilizumab group, further complicating direct efficacy comparisons.

In light of these concerns, we suggest that future studies consider using SOFA or APACHE II scores in PSM to better control for baseline severity differences. If SOFA or APACHE II data are unavailable, matching based on laboratory data associated with SOFA or APACHE II scores at the time of ICU admission or intubation could serve as a proxy for disease severity [5,6,7]. Incorporating these variables may help mitigate confounding and strengthen the conclusions. Additionally, more detailed time-dependent analyses, such as the duration of mechanical ventilation or timing of drug administration, would clarify the true effects of these therapies in critically ill patients.

Ultimately, randomized controlled trials remain the gold standard to address these concerns, but in the interim, the use of more nuanced statistical matching techniques may help refine comparisons between baricitinib and tocilizumab in this population.

No datasets were generated or analysed during the current study.

  1. You S-H, Baek MS, Kim TW, Jung S-Y, Kim W-Y. Baricitinib versus tocilizumab in mechanically ventilated patients with COVID–19: a nationwide cohort study. Crit Care. 2024;28(1):282.

    Article PubMed PubMed Central Google Scholar

  2. Liu LT, Tsai JJ. Unveiling COVID–19 treatment strategies for immunocompromised individuals: terapeutic innovations and latest findings. Hoboken: Wiley; 2024. p. e14900.

    Google Scholar

  3. Trøseid M, Arribas JR, Assoumou L, Holten AR, Poissy J, Terzić V, et al. Efficacy and safety of baricitinib in hospitalized adults with severe or critical COVID–19 (Bari-SolidAct): a randomised, double-blind, placebo-controlled phase 3 trial. Crit Care. 2023;27(1):9.

    Article PubMed PubMed Central Google Scholar

  4. Lopez-Delgado JC, Servia-Goixart L, Grau-Carmona T, Bordeje-Laguna L, Portugal-Rodriguez E, Lorencio-Cardenas C, et al. Factors associated with the need of parenteral nutrition in critically ill patients after the initiation of enteral nutrition therapy. Front Nutr. 2023;10:1250305.

    Article PubMed PubMed Central Google Scholar

  5. Vicka V, Januskeviciute E, Miskinyte S, Ringaitiene D, Serpytis M, Klimasauskas A, et al. Comparison of mortality risk evaluation tools efficacy in critically ill COVID–19 patients. BMC Infect Dis. 2021;21:1–7.

    Article Google Scholar

  6. Beigmohammadi MT, Amoozadeh L, Rezaei Motlagh F, Rahimi M, Maghsoudloo M, Jafarnejad B, et al. Mortality predictive value of APACHE II and SOFA scores in COVID–19 patients in the intensive care unit. Can Respir J. 2022;2022(1):5129314.

    PubMed PubMed Central Google Scholar

  7. Roddy J, Wells D, Schenck K, Santosh S, Santosh S. Tocilizumab versus baricitinib in patients hospitalized with COVID–19 pneumonia and hypoxemia: a multicenter retrospective cohort study. Crit Care Explor. 2022;4(5):e0702.

    Article PubMed PubMed Central Google Scholar

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Authors and Affiliations

  1. Department of Allergy, Immunology & Rheumatology, Chung Shan Medical University Hospital, Section 1, Jianguo N Rd, Taichung, 402, Taiwan

    James Cheng Chung Wei

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

    James Cheng Chung Wei & Po-Cheng Shih

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

    James Cheng Chung Wei

  4. Chung Shan Medical University Hospital, Taichung, Taiwan

    Poi Kuo

  5. Department of Allergy, Immunology & Rheumatology, Changhua Christian Hospital, Changhua, Taiwan

    Po-Cheng Shih

  6. Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, 030032, China

    James Cheng Chung Wei

  7. Institute of Medicine/Department of Nursing, Chung Shan Medical University, Taichung, Taiwan

    James Cheng Chung Wei

Authors
  1. James Cheng Chung WeiView author publications

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  2. Poi KuoView author publications

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  3. Po-Cheng ShihView author publications

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Contributions

All authors wrote and revised the manuscript.

Corresponding author

Correspondence to Po-Cheng Shih.

Conflict of interest

The authors declare no competing interests.

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Wei, J.C.C., Kuo, P. & Shih, PC. Commenting on baricitinib versus tocilizumab in mechanically ventilated patients with COVID-19: a nationwide cohort study. Crit Care 28, 357 (2024). https://doi.org/10.1186/s13054-024-05116-6

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来源期刊
Critical Care
Critical Care 医学-危重病医学
CiteScore
20.60
自引率
3.30%
发文量
348
审稿时长
1.5 months
期刊介绍: Critical Care is an esteemed international medical journal that undergoes a rigorous peer-review process to maintain its high quality standards. Its primary objective is to enhance the healthcare services offered to critically ill patients. To achieve this, the journal focuses on gathering, exchanging, disseminating, and endorsing evidence-based information that is highly relevant to intensivists. By doing so, Critical Care seeks to provide a thorough and inclusive examination of the intensive care field.
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