The outcome of patients with Severe COVID 19 treated with tocilizumab:a Retrospective Cohort study
Main Article Content
Keywords
Coronavirus disease 19, Assisted/invasive mechanical ventilation, Tocilizumab, Intensive care unit, mortality.
Abstract
BACKGROUND
Coronavirus disease 2019 triggers a cytokine storm resulting in high mortality. A key player in this cytokine storm has been considered as interleukin-6. Tocilizumab, a monoclonal antibody, is theorized to treat COVID-19 by inhibiting the interleukin-6 receptor. However, conflicting data supporting this hypothesis is available in the literature.
METHODOLOGY
This retrospective cohort included 1001 severe COVID-19 patients from a tertiary care hospital, Pakistan, hospitalized from March 2020 to August 2021. Primary outcome was the proportion of patients expired. Beside proportion of patients discharged, requirements for assisted ventilation and ICU admission were other outcomes. We also saw the impact of tocilizumab on radiological findings, oxygenation, and inflammatory markers.
RESULTS
Of 100 patients in the toci group, 85(85%) patients were ultimately discharged, compared to only 57.9% patients in R-toci and 62.9% patients in SOC group were discharged (p < 0.001). Fifty-nine (38.8%) patients in R-toci group and one hundred ninety-six (26.2%) patients in SOC group were expired in comparison to toci group in which only eight (8%) of patients were expired (p < 0.001). Similarly need for invasive mechanical ventilation and ICU admission remained lowest in toci group. Improvement in radiological findings, oxygenation, and inflammatory markers was observed after using tocilizumab. Patients receiving standard of care had lowest survival. Among discharge patients, those who received standard of care had longest hospital stay.
CONCLUSION
Tocilizumab use in patients with severe COVID-19 is associated with a significant reduction in mortality, need for ICU admission and invasive mechanical ventilation.
References
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18. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet. 2020;395(10223):497-506.
19. Lagunas-Rangel FA, Chávez-Valencia V. High IL-6/IFN-γ ratio could be associated with severe disease in COVID-19 patients. J Med Virol. 2020;92(10):1789-90.
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22. Xu X, Han M, Li T, Sun W, Wang D, Fu B, et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci U S A. 2020;117(20):10970-5.
23. Sánchez-Rovira P, Pérez-Chica G, Ortega-Granados AL, Aguilar-García J, Díaz-Beltrán L, Gálvez-Montosa F, et al. Early use of tocilizumab in patients with severe pneumonia secondary to severe acute respiratory syndrome coronavirus 2 infection and poor prognostic criteria: Impact on mortality rate and intensive care unit admission. Medicine. 2021;100(29):e26533.
24. Xu X, Han M, Li T, Sun W, Wang D, Fu B, et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proceedings of the National Academy of Sciences. 2020;117(20):10970-5.
25. Bhatraju PK, Ghassemieh BJ, Nichols M, Kim R, Jerome KR, Nalla AK, et al. Covid-19 in Critically Ill Patients in the Seattle Region — Case Series. New England Journal of Medicine. 2020;382(21):2012-22.
26. Kewan T, Covut F, Al–Jaghbeer MJ, Rose L, Gopalakrishna KV, Akbik B. Tocilizumab for treatment of patients with severe COVID–19: A retrospective cohort study. EClinicalMedicine. 2020;24.
27. Ramaswamy M, Mannam P, Comer R, Sinclair E, McQuaid DB, Schmidt ML. Off-Label Real World Experience Using Tocilizumab for Patients Hospitalized with COVID-19 Disease in a Regional Community Health System: A Case-Control Study. medRxiv. 2020:2020.05.14.20099234.
28. Quartuccio L, Sonaglia A, McGonagle D, Fabris M, Peghin M, Pecori D, et al. Profiling COVID-19 pneumonia progressing into the cytokine storm syndrome: Results from a single Italian Centre study on tocilizumab versus standard of care. J Clin Virol. 2020;129:104444.
29. Luo P, Liu Y, Qiu L, Liu X, Liu D, Li J. Tocilizumab treatment in COVID-19: A single center experience. Journal of medical virology. 2020;92(7):814-8.
30. Alattar R, Ibrahim TBH, Shaar SH, Abdalla S, Shukri K, Daghfal JN, et al. Tocilizumab for the treatment of severe coronavirus disease 2019. Journal of medical virology. 2020;92(10):2042-9.
31. Rezaei S, Fatemi B, Karimi Majd Z, Minaei H, Peikanpour M, Anjidani N, et al. Efficacy and safety of Tocilizumab in severe and critical COVID-19: A Systematic Review and Meta-Analysis. Expert Rev Clin Immunol. 2021;17(5):499-511.
32. Rubio-Rivas M, Mora-Luján JM, Montero A, Homs NA, Rello J, Corbella X. Beneficial and harmful outcomes of tocilizumab in severe COVID-19: a systematic review and meta-analysis. medRxiv. 2020:2020.09.05.20188912.
33. Khan F, Stewart I, Fabbri L, Moss S, Robinson KA, Smyth A, et al. A systematic review and meta-analysis of Anakinra, Sarilumab, Siltuximab and Tocilizumab for Covid-19. medRxiv. 2021:2020.04.23.20076612.
34. Kotak S, Khatri M, Malik M, Malik M, Hassan W, Amjad A, et al. Use of Tocilizumab in COVID-19: A Systematic Review and Meta-Analysis of Current Evidence. Cureus. 2020;12(10):e10869.
35. Sarfraz A, Sarfraz Z, Sarfraz M, Aftab H, Pervaiz Z. Tocilizumab and COVID-19: a meta-analysis of 2120 patients with severe disease and implications for clinical trial methodologies. Turk J Med Sci. 2021;51(3):890-7.
36. Zhao M, Lu J, Tang Y, Dai Y, Zhou J, Wu Y. Tocilizumab for treating COVID-19: a systemic review and meta-analysis of retrospective studies. Eur J Clin Pharmacol. 2021;77(3):311-9.
37. Tsai A, Diawara O, Nahass RG, Brunetti L. Impact of tocilizumab administration on mortality in severe COVID-19. Scientific Reports. 2020;10(1):19131.
38. Knorr JP, Colomy V, Mauriello CM, Ha S. Tocilizumab in patients with severe COVID-19: A single-center observational analysis. Journal of Medical Virology. 2020;92(11):2813-20.
39. Stone JH, Frigault MJ, Serling-Boyd NJ, Fernandes AD, Harvey L, Foulkes AS, et al. Efficacy of Tocilizumab in Patients Hospitalized with Covid-19. New England Journal of Medicine. 2020;383(24):2333-44.
40. 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(8):e474-e84.
41. Roumier M, Paule R, Groh M, Vallée A, Ackermann F, Group ftFC-S. Interleukin-6 blockade for severe COVID-19. medRxiv. 2020:2020.04.20.20061861.
42. Campochiaro C, Della-Torre E, Cavalli G, De Luca G, Ripa M, Boffini N, et al. Efficacy and safety of tocilizumab in severe COVID-19 patients: a single-centre retrospective cohort study. European Journal of Internal Medicine. 2020;76:43-9.
43. Morena V, Milazzo L, Oreni L, Bestetti G, Fossali T, Bassoli C, et al. Off-label use of tocilizumab for the treatment of SARS-CoV-2 pneumonia in Milan, Italy. European Journal of Internal Medicine. 2020;76:36-42.
2. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054-62.
3. Guan W-j, Ni Z-y, Hu Y, Liang W-h, Ou C-q, He J-x, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. New England Journal of Medicine. 2020;382(18):1708-20.
4. Nicastri E, D'Abramo A, Faggioni G, De Santis R, Mariano A, Lepore L, et al. Coronavirus disease (COVID-19) in a paucisymptomatic patient: epidemiological and clinical challenge in settings with limited community transmission, Italy, February 2020. Euro Surveill. 2020;25(11).
5. Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, et al. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020;130(5):2620-9.
6. Schaller T, Hirschbühl K, Burkhardt K, Braun G, Trepel M, Märkl B, et al. Postmortem Examination of Patients With COVID-19. Jama. 2020;323(24):2518-20.
7. Coomes EA, Haghbayan H. Interleukin-6 in Covid-19: A systematic review and meta-analysis. Rev Med Virol. 2020;30(6):1-9.
8. Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, et al. A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19. New England Journal of Medicine. 2020;382(19):1787-99.
9. Stebbing J, Phelan A, Griffin I, Tucker C, Oechsle O, Smith D, et al. COVID-19: combining antiviral and anti-inflammatory treatments. The Lancet Infectious Diseases. 2020;20(4):400-2.
10. Alattar R, Ibrahim TBH, Shaar SH, Abdalla S, Shukri K, Daghfal JN, et al. Tocilizumab for the treatment of severe coronavirus disease 2019. J Med Virol. 2020;92(10):2042-9.
11. Parr JB. Time to Reassess Tocilizumab’s Role in COVID-19 Pneumonia. JAMA Internal Medicine. 2021;181(1):12-5.
12. Luo P, Liu Y, Qiu L, Liu X, Liu D, Li J. Tocilizumab treatment in COVID-19: A single center experience. J Med Virol. 2020;92(7):814-8.
13. Radbel J, Narayanan N, Bhatt PJ. Use of Tocilizumab for COVID-19-Induced Cytokine Release Syndrome: A Cautionary Case Report. Chest. 2020;158(1):e15-e9.
14. Sciascia S, Aprà F, Baffa A, Baldovino S, Boaro D, Boero R, et al. Pilot prospective open, single-arm multicentre study on off-label use of tocilizumab in patients with severe COVID-19. Clin Exp Rheumatol. 2020;38(3):529-32.
15. Klopfenstein T, Zayet S, Lohse A, Balblanc JC, Badie J, Royer PY, et al. Tocilizumab therapy reduced intensive care unit admissions and/or mortality in COVID-19 patients. Med Mal Infect. 2020;50(5):397-400.
16. Toniati P, Piva S, Cattalini M, Garrafa E, Regola F, Castelli F, et al. Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: A single center study of 100 patients in Brescia, Italy. Autoimmun Rev. 2020;19(7):102568.
17. Wu C, Chen X, Cai Y, Xia Ja, Zhou X, Xu S, et al. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Internal Medicine. 2020;180(7):934-43.
18. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet. 2020;395(10223):497-506.
19. Lagunas-Rangel FA, Chávez-Valencia V. High IL-6/IFN-γ ratio could be associated with severe disease in COVID-19 patients. J Med Virol. 2020;92(10):1789-90.
20. Kimura A, Kishimoto T. IL-6: regulator of Treg/Th17 balance. European journal of immunology. 2010;40(7):1830-5.
21. Liu B, Li M, Zhou Z, Guan X, Xiang Y. Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)? Journal of autoimmunity. 2020;111:102452.
22. Xu X, Han M, Li T, Sun W, Wang D, Fu B, et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci U S A. 2020;117(20):10970-5.
23. Sánchez-Rovira P, Pérez-Chica G, Ortega-Granados AL, Aguilar-García J, Díaz-Beltrán L, Gálvez-Montosa F, et al. Early use of tocilizumab in patients with severe pneumonia secondary to severe acute respiratory syndrome coronavirus 2 infection and poor prognostic criteria: Impact on mortality rate and intensive care unit admission. Medicine. 2021;100(29):e26533.
24. Xu X, Han M, Li T, Sun W, Wang D, Fu B, et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proceedings of the National Academy of Sciences. 2020;117(20):10970-5.
25. Bhatraju PK, Ghassemieh BJ, Nichols M, Kim R, Jerome KR, Nalla AK, et al. Covid-19 in Critically Ill Patients in the Seattle Region — Case Series. New England Journal of Medicine. 2020;382(21):2012-22.
26. Kewan T, Covut F, Al–Jaghbeer MJ, Rose L, Gopalakrishna KV, Akbik B. Tocilizumab for treatment of patients with severe COVID–19: A retrospective cohort study. EClinicalMedicine. 2020;24.
27. Ramaswamy M, Mannam P, Comer R, Sinclair E, McQuaid DB, Schmidt ML. Off-Label Real World Experience Using Tocilizumab for Patients Hospitalized with COVID-19 Disease in a Regional Community Health System: A Case-Control Study. medRxiv. 2020:2020.05.14.20099234.
28. Quartuccio L, Sonaglia A, McGonagle D, Fabris M, Peghin M, Pecori D, et al. Profiling COVID-19 pneumonia progressing into the cytokine storm syndrome: Results from a single Italian Centre study on tocilizumab versus standard of care. J Clin Virol. 2020;129:104444.
29. Luo P, Liu Y, Qiu L, Liu X, Liu D, Li J. Tocilizumab treatment in COVID-19: A single center experience. Journal of medical virology. 2020;92(7):814-8.
30. Alattar R, Ibrahim TBH, Shaar SH, Abdalla S, Shukri K, Daghfal JN, et al. Tocilizumab for the treatment of severe coronavirus disease 2019. Journal of medical virology. 2020;92(10):2042-9.
31. Rezaei S, Fatemi B, Karimi Majd Z, Minaei H, Peikanpour M, Anjidani N, et al. Efficacy and safety of Tocilizumab in severe and critical COVID-19: A Systematic Review and Meta-Analysis. Expert Rev Clin Immunol. 2021;17(5):499-511.
32. Rubio-Rivas M, Mora-Luján JM, Montero A, Homs NA, Rello J, Corbella X. Beneficial and harmful outcomes of tocilizumab in severe COVID-19: a systematic review and meta-analysis. medRxiv. 2020:2020.09.05.20188912.
33. Khan F, Stewart I, Fabbri L, Moss S, Robinson KA, Smyth A, et al. A systematic review and meta-analysis of Anakinra, Sarilumab, Siltuximab and Tocilizumab for Covid-19. medRxiv. 2021:2020.04.23.20076612.
34. Kotak S, Khatri M, Malik M, Malik M, Hassan W, Amjad A, et al. Use of Tocilizumab in COVID-19: A Systematic Review and Meta-Analysis of Current Evidence. Cureus. 2020;12(10):e10869.
35. Sarfraz A, Sarfraz Z, Sarfraz M, Aftab H, Pervaiz Z. Tocilizumab and COVID-19: a meta-analysis of 2120 patients with severe disease and implications for clinical trial methodologies. Turk J Med Sci. 2021;51(3):890-7.
36. Zhao M, Lu J, Tang Y, Dai Y, Zhou J, Wu Y. Tocilizumab for treating COVID-19: a systemic review and meta-analysis of retrospective studies. Eur J Clin Pharmacol. 2021;77(3):311-9.
37. Tsai A, Diawara O, Nahass RG, Brunetti L. Impact of tocilizumab administration on mortality in severe COVID-19. Scientific Reports. 2020;10(1):19131.
38. Knorr JP, Colomy V, Mauriello CM, Ha S. Tocilizumab in patients with severe COVID-19: A single-center observational analysis. Journal of Medical Virology. 2020;92(11):2813-20.
39. Stone JH, Frigault MJ, Serling-Boyd NJ, Fernandes AD, Harvey L, Foulkes AS, et al. Efficacy of Tocilizumab in Patients Hospitalized with Covid-19. New England Journal of Medicine. 2020;383(24):2333-44.
40. 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(8):e474-e84.
41. Roumier M, Paule R, Groh M, Vallée A, Ackermann F, Group ftFC-S. Interleukin-6 blockade for severe COVID-19. medRxiv. 2020:2020.04.20.20061861.
42. Campochiaro C, Della-Torre E, Cavalli G, De Luca G, Ripa M, Boffini N, et al. Efficacy and safety of tocilizumab in severe COVID-19 patients: a single-centre retrospective cohort study. European Journal of Internal Medicine. 2020;76:43-9.
43. Morena V, Milazzo L, Oreni L, Bestetti G, Fossali T, Bassoli C, et al. Off-label use of tocilizumab for the treatment of SARS-CoV-2 pneumonia in Milan, Italy. European Journal of Internal Medicine. 2020;76:36-42.
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Jul 6, 2023
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Jamil Muqtadir Bhatti,Syed Ali Raza,Noshirwan P.Gazder,Khizer Shamim,FNU Sameeullah,Irshad Batool Abro. (2023). The outcome of patients with Severe COVID 19 treated with tocilizumab:a Retrospective Cohort study. Journal of Population Therapeutics and Clinical Pharmacology, 30(6), 463–478. https://doi.org/10.53555/jptcp.v30i6.2335
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