We read with interest the article titled “Letter to Editor in response to article ‘Efficacy of Tocilizumab in treatment of COVID-19 pneumonia: A case–control study from a tertiary care hospital’ published in Lung India.” We have the following comments to offer:
- Since tocilizumab was costly, not easily available during the pandemic and had significant adverse effects, its usage was based on criteria comprising clinical and laboratory markers and radiological opacities. These criteria were not uniform and were based on a few studies[2,3] published during the period of this study and quoted by the authors. In this study, the authors have not specified any such criteria or guidelines for intervention with tocilizumab. Also, during the time period of this study, tocilizumab was used in moderate, severe and critical patients and rapidly progressive cases in studies from abroadand in India. It is not understood how tocilizumab was used in 13 mild cases in this study. Moreover, mortality in mild cases and control was 6.25% and 7.5%, respectively, in this study. This unusually high mortality rate in mild cases needs further elaboration.
- The authors have calculated the inflammatory score based on biological reference interval, which does not give a proper correlation of disease severity with inflammatory markers. Since there were data available for various inflammatory markers in this retrospective study, the authors should have either used mean values with standard deviation using their own data or used the weighted mean difference values mentioned in a meta-analysis by Zeng F, et al., which has been quoted as a reference in this study.
- The authors have found better outcomes with tocilizumab with an inflammatory score of less than 3 in this study and have concluded that a lower level of inflammatory score may be used as a predictor of outcome with tocilizumab. In the discussion, the authors have supported this finding by quoting a study by Olewicz-Gawlik et al. In fact, this referenced study has not been interpreted correctly. In this study, the serum concentrations of inflammatory markers before the administration of tocilizumab did not predict the outcome, whereas interleukin-6 (IL-6) and lactate dehydrogenase (LDH) measurements after the administration of tocilizumab seemed to be of predictive value. Because higher levels of inflammatory markers, especially C-reactive protein (CRP) and IL-6, are associated with poor outcome and CRP levels above 75 mg/ml are taken as one of the criteria for initiating treatment with tocilizumab, this contrasting finding in this study needs elaboration.
- The study has found the role of tocilizumab in reducing mortality in those with low Sequential Organ Failure Assessment (SOFA) score. The authors have quoted a study by Guaraldi G et al., in support of this observation. In fact, this study has adjusted SOFA score between cases and controls for the assessment of the efficacy of tocilizumab and does not mention the correlation of low SOFA score with reduced mortality. This requires further elaboration by the authors.
- Tocilizumab has significant adverse effects, and the same has not been studied with no mention of adverse effects and overall safety.
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Conflicts of interest
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1. Minal Shastri, Darshankumar Manubhai Raval, Ummayhany Fakhruddin Bharmal, et al. Efficacy of tocilizumab in treatment of COVID-19 pneumonia:A case–control study from a tertiary care hospital. Lung India 2022;39:510–6.
2. Radulescu A, Istrate A, Muntean M. Treatment with tocilizumab in adult patients with moderate to critical COVID-19 pneumonia:A single-center retrospective study. Int J Infect Dis 2022;117:1–7.
3. Gokhale Y, Mehta R, Kulkarni U, Karnik N, Gokhale S, Sundar U, et al. Tocilizumab improves survival in severe COVID-19 pneumonia with persistent hypoxia:A retrospective cohort study with follow-up from Mumbai, India. BMC Infect Dis 2021;21:241.
4. Zeng F, Huang Y, Guo Y, Yin M, Chen X, Xiao L, et al. Association of inflammatory markers with the severity of COVID-19:A meta-analysis. Int J Infect Dis 2020;96:467–74.
5. Olewicz-Gawlik A, Ginter-Matuszewska B, Kamiński M, Adamek A, Bura M, Mozer-Lisewska I, et al. Changes in inflammatory markers after administration of tocilizumab in COVID-19:A single-center retrospective study. J Clin Med 2021;11:107.
6. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ HLH AcrossSpeciality Collaboration UK Lancet 2020;395 10229:1033 Epub 2020 Mar 16.
7. National Health Service Interleukin-6 inhibitors (tocilizumab or sarilumab) for hospitalised patients with COVID-19 pneumonia (adults) February 17 2021.
8. Guaraldi G, Meschiari M, Cozzi-Lepri A, Milic J, Tonelli R, Menozzi M, et al. Tocilizumab in patients with severe COVID-19:A retrospective cohort study. Lancet Rheumatol 2020;2:e474–84.