ROLE OF TOCILIZUMAB IN PATIENTS WITH MODERATE-TO-SEVERE COVID-19 PNEUMONIA
DOI:
https://doi.org/10.22159/ajpcr.2022.v15i11.45609Keywords:
COVID-19, Cytokine release syndrome, Interleukin-6, Mortality, TocilizumabAbstract
Objectives: Cytokine release syndrome (CRS) is believed to be responsible for death in COVID-19. Tocilizumab is an interleukin (IL)-6 receptor antagonist, IL-6 being identified as a major component of the CRS cascade. The objective of the study was to determine if tocilizumab can prevent mortality and morbidity in moderate-to-severe COVID-19 pneumonia.
Methods: Patients admitted to the ICU between the time period of June 2020–August 2020 were included in this retrospective and cohort study conducted at GCS medical college, hospital and research center. Patients had to be more than 18 years of age and were required to have a positive reverse transcription polymerase chain reaction report for COVID-19. After applying the inclusion/exclusion criteria, 119 patients were considered for final analysis. Tocilizumab was administered as a single dose of 8 mg/kg in 22 patients. Rest of the patients received standard of care regime. The primary outcome was either discharge or death of the patients and the requirement of invasive mechanical ventilation during their hospital stay. The secondary outcome was the length of hospital stay. Appropriate demographic, clinical, and laboratory data were documented. Statistical analysis was done with appropriate clinical tests with significance set at p<0.05.
Results: Tocilizumab significantly reduced deaths in patients as well as the need for mechanical ventilation with NNT=3 and 5, respectively. The same held true even when the data were adjusted for age, gender, and number of comorbidities. Number of comorbidities had a negative association with mortality and need for mechanical ventilation irrespective of administration of tocilizumab as evidenced by multivariable logistic regression. There was no effect of tocilizumab in shortening the hospital stay in patients.
Conclusion: Tocilizumab seems to be a promising agent for the treatment of moderate to severe COVID-19 pneumonia and similar agents hold promise for any similar future emerging infections.
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References
Johns Hopkins University. COVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University. Maryland: Johns Hopkins University 2022.
RECOVERY Collaborative Group, Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, et al. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med 2021;384:693-704. doi: 10.1056/ NEJMoa2021436, PMID 32678530
De Roquetaillade C, Bredin S, Lascarrou JB, Soumagne T, Cojocaru M, Chousterman BG, et al. Timing and causes of death in severe COVID-19 patients. Crit Care 2021;25:224. doi: 10.1186/s13054-021- 03639-w, PMID 34193220
Hojyo S, Uchida M, Tanaka K, Hasebe R, Tanaka Y, Murakami M, et al. How COVID-19 induces cytokine storm with high mortality. Inflamm Regen 2020;40:37. doi: 10.1186/s41232-020-00146-3, PMID 33014208
Giamarellos-Bourboulis EJ, Netea MG, Rovina N, Akinosoglou K, Antoniadou A, Antonakos N, et al. Complex immune dysregulation in COVID-19 patients with severe respiratory failure. Cell Host Microbe 2020;27:992-1000.e3. doi: 10.1016/j.chom.2020.04.009, PMID 32320677
Blanco-Melo D, Nilsson-Payant BE, Liu WC, Uhl S, Hoagland D, Møller R, et al. Imbalanced host response to SARS-CoV-2 drives development of COVID-19. Cell 2020;181:1036-45.e9. doi: 10.1016/j. cell.2020.04.026, PMID 32416070
Mihara M, Ohsugi Y, Kishimoto T. Tocilizumab, a humanized anti-interleukin-6 receptor antibody, for treatment of rheumatoid arthritis. Open Access Rheumatol 2011;3:19-29. doi: 10.2147/OARRR.S17118, PMID 27790001
Rubbert-Roth A, Furst DE, Nebesky JM, Jin A, Berber E. A review of recent advances using tocilizumab in the treatment of rheumatic diseases. Rheumatol Ther 2018;5:21-42. doi: 10.1007/s40744-018- 0102-x, PMID 29502236
Guidelines on Clinical Management of COVID-19 v.3. Ministry of Health and Family Welfare, Government of India. 2022. Available from: https://www. mohfw.gov.in/pdf/ClinicalGuidanceforManagementofAdultCovid19Patients [Last accessed on 2022 Jun 13].
Nasa P, Singh A, Upadhyay S, Bagadia S, Polumuru S, Shrivastava PK, et al. Tocilizumab use in COVID-19 cytokine-release syndrome: Retrospective study of two centers. Indian J Crit Care Med 2020;24:771-6. doi: 10.5005/jp-journals-10071-23566, PMID 33132558
Shastri M, Raval DM, Rathod VM, Patel D. Adjuvant tocilizumab in the treatment of patients with moderate to severe COVID-19 pneumonia: An observational study. J Assoc Physicians India 2022;70:11-2.
Tleyjeh IM, Kashour Z, Damlaj M, Riaz M, Tlayjeh H, Altannir M, et al. Efficacy and safety of tocilizumab in COVID-19 patients: A living systematic review and meta-analysis. Clin Microbiol Infect 2021;27:215-27. doi: 10.1016/j.cmi.2020.10.036, PMID 33161150
Aziz M, Haghbin H, Sitta EA, Nawras Y, Fatima R, Sharma S, et al. Efficacy of tocilizumab in COVID-19: A systematic review and meta-analysis. J Med Virol 2021;93:1620-30. doi: 10.1002/jmv.26509, PMID 32918755
Biran N, Ip A, Ahn J, Go RC, Wang S, Mathura S, et al. Tocilizumab among patients with COVID-19 in the intensive care unit: A multicentre observational study. Lancet Rheumatol 2020;2:e603-12. doi: 10.1016/ S2665-9913(20)30277-0, PMID 32838323
Angus DC, Berry S, Lewis RJ, Al-Beidh F, Arabi Y, van Bentum-Puijk W, et al. The REMAP-CAP (randomized embedded multifactorial adaptive platform for community-acquired pneumonia) study. Rationale and design. Ann Am Thorac Soc 2020;17:879-91. doi: 10.1513/AnnalsATS.202003-192SD, PMID 32267771
Salama C, Han J, Yau L, Reiss WG, Kramer B, Neidhart JD, et al. Tocilizumab in patients hospitalized with Covid-19 pneumonia. N Engl J Med 2021;384:20-30. doi: 10.1056/NEJMoa2030340, PMID 33332779
Rosas IO, Bräu N, Waters M, Go RC, Hunter BD, Bhagani S, et al. Tocilizumab in hospitalized patients with severe Covid-19 pneumonia. N Engl J Med 2021;384:1503-16. doi: 10.1056/NEJMoa2028700, PMID 33631066
RECOVERY Collaborative Group. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): A randomised, controlled, open-label, platform trial. Lancet 2021;397:1637-45. doi: 10.1016/ S0140-6736(21)00676-0, PMID 33933206
Salvarani C, Dolci G, Massari M, Merlo DF, Cavuto S, Savoldi L, et al. Effect of tocilizumab vs standard care on clinical worsening in patients hospitalized with COVID-19 pneumonia: A randomized clinical trial. JAMA Intern Med 2021;181:24-31. doi: 10.1001/ jamainternmed.2020.6615, PMID 33080005
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