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VOLUME 26 , ISSUE 10 ( October, 2022 ) > List of Articles

Original Article

Comparison of Anakinra and Tocilizumab in Anticytokine Therapy in the Treatment of Coronavirus Disease-2019

Feyza Ozkan, Süleyman Sari

Keywords : Anakinra, Coronavirus disease-2019, Cytokine, Tocilizumab

Citation Information : Ozkan F, Sari S. Comparison of Anakinra and Tocilizumab in Anticytokine Therapy in the Treatment of Coronavirus Disease-2019. Indian J Crit Care Med 2022; 26 (10):1091-1098.

DOI: 10.5005/jp-journals-10071-24320

License: CC BY-NC 4.0

Published Online: 30-09-2022

Copyright Statement:  Copyright © 2022; The Author(s).


Abstract

Background: It is known that coronavirus disease-2019 (COVID-19) pneumonia causes cytokine storm, and treatment modalities are being developed on inhibition of proinflammatory cytokines. We aimed to investigate the effects of anticytokine therapy on clinical improvement and the differences between anticytokine treatments. Materials and methods: A total of 90 patients with positive COVID-19 polymerase chain reaction (PCR) test were divided into three groups, group I (n = 30) was given anakinra, group II (n = 30) was given tocilizumab, and group III (n = 30) was given standard treatment. Group I was treated with anakinra for 10 days; tocilizumab, intravenously, was given in group II. Group III patients were selected from those who did not receive any anticytokine treatment other than the standard treatment. Laboratory values, Glasgow coma scale (GCS), and PaO2/FiO2 values were analyzed on days 1, 7, and 14. Results: The seventh-day mortality rates were 6.7% in group II, 23.3% in group I, and 16.7% in group III. In group II, the ferritin levels on the 7th and 14th days were significantly lower (p = 0.004), and the lymphocyte levels on the seventh day were significantly higher (p = 0.018). Examining the changes between the first intubation days, in the early period (seventh day), group I was found to be 21.7%, group II was 26.9%, and group III was 47.6%. Conclusion: We observed the positive effects of the use of tocilizumab on clinical improvement in the early period; mechanical ventilation requirement was delayed and at a lower rate. Anakinra treatment did not change mortality and PaO2/FiO2 rates. Mechanical ventilation requirements occurred earlier in the patients who were not receiving any anticytokine therapy. Studies with larger patient populations are needed to demonstrate the potential efficacy of anticytokine therapy.


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  1. 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): 1054–1062. DOI: 10.1016/S0140-6736(20)30566-3.
  2. Yücel AA, Bayrakal V, Baskin H, Cytokine storm and COVID-19. In: Immunology and COVID-19. Ankara, Türkiye Klinikleri, 2020, pp.15–21.
  3. Herold T, Jurinovic V, Arnreich C, Lipworth BJ, Hellmuth JC, von Bergwelt–Baildon M et al. Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19. J Allergy Clin Immunol 2020;146(1):128.36.e4. DOI: 10.1016/j.jaci.2020.05.008.
  4. Zhu J, Pang J, Ji P, Zhong Z, Li H, Li B, et al. Elevated interleukin-6 is associated with severity of COVID-19: A meta-analysis. J Med Virol 2021;93(1):35–37. DOI: 10.1002/jmv.26085.
  5. Declercq J, Damme KFAV, Leeuw ED, Maes B, Bosteels C, Tavernier SJ, et al. Effect of anti-interleukin drugs in patients with COVID-19 and signs of cytokine release syndrome (COV–AID): A factorial, randomised, controlled trial, Lancet Respir Med 2021;9(12):1427–1438. DOI: 10.1016/S2213-2600(21)00377-5.
  6. Metha P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ, et al. COVID-19: Consider cytokine storm syndromes and immunosuppression. Lancet 2020;395:1033–1034. DOI: 10.1016/S0140-6736(20)30628-0.
  7. Henderson LA, Canna SW, Schulert GS, Volpi S, Lee PY, Kernan KF, et al. On the alert for cytokine storm: Immunopathology in COVID-19. Arthritis Rheumatol 2020;72(7):1059–1063. DOI: 10.1002/art.41285.
  8. Dinarello CA. Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood 2010;117(14):3720–3732. DOI: 10.1182/blood-2010-07-273417.
  9. Opal SM, Fisher CJ Jr, Dhainaut JF, Vincent JL, Brase R, Lowry SF, et al. Confirmatory interleukin-1 receptor antagonist trial in severe sepsis: A phase III, randomized, double-blind, placebo-controlled, multicenter trial. Crit Care Med 1997;25(7):1115–1124. DOI: 10.1097/00003246-199707000-00010.
  10. Zhang X, Georgy A, Rowell L. Pharmacokinetics and pharmacodynamics of tocilizumab, a humanized anti-interleukin-6 receptor monoclonal antibody, following single-dose administration by subcutaneous and intravenous routes to healthy subjects. Int J Clin Pharmacol Ther 2013;51(6):443–455. DOI:10.5414/CP201819.
  11. Nishimoto N, Yoshizaki K, Maeda K, Kuritani T, Deguchi H, Sato B, et al. Toxicity, pharmacokinetics, and dose-finding study of repetitive treatment with the humanized anti-interleukin 6 receptor antibody MRA in rheumatoid arthritis. Phase I/II clinical study. J Rheumatol 2003;30(7):1426–1435. PMID: 12858437.
  12. Della–Torre E, Campochiaro C, Cavalli G, Luca GD, Napolitano A, Marca SL, et al. Interleukin-6 blockade with sarilumab in severe COVID-19 pneumonia with systemic hyperinflammation: An open-label cohort study. Ann Rheum Dis 2020;79(10):1277–1285. DOI: 10.1136/annrheumdis-2020-218122.
  13. Della–Torre E, Campochiaro C, Cavalli G, Luca DG, Ciceri F, Zangrillo A, et al. Targeting IL-1, IL-6 or GM-CSF in COVID-19. Response to: ‘More evidences on which biologic and which pathway is key in severe-critical COVID-19 pneumonia’ by Ferraccioli. Ann Rheum Dis 2020; annrheumdis-2020-218612. DOI: 10.1056/NEJMoa2028836.
  14. 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. Eur J Intern Med 2020;76:43–49. DOI: 10.1016/j.ejim.2020.05.021.
  15. Kyriazopoulou E, Panagopoulos P, Metallidis S, Dalekos GN, Poulakou G, Gatselis N, et al. An open label trial of anakinra to prevent respiratory failure in COVID-19, Elife 2021;10:e66125. DOI: 10.7554/eLife.66125.
  16. Cavalli G, Luca GD, Campochiaro C, Della–Torre E, Marco Ripa, Diana Canetti, et al. Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: A retrospective cohort study, Lancet Rheumatol 2020;2(6):e325–e331. DOI: 10.1016/S2665-9913(20)30127-2.
  17. Pontali E, Volpi S, Signori A, Antonucci G, Castellaneta M, Buzzi D, et al. Efficacy of early anti-inflammatory treatment with high doses of intravenous anakinra with or without glucocorticoids in patients with severe COVID-19 pneumonia. J Allergy Clin Immunol. 2021;147(4):1217–1225. DOI: 10.1016/j.jaci.2021.01.024.
  18. Kharazmi AB, Moradi O, Haghighi M, Küçücük MM, Rasi AM, Raoufi M, et al. A randomized controlled clinical trial on efficacy and safety of anakinra in patients with severe COVID-19. Immun Inflamm Dis 2022;10(2):201–208. DOI: 10.1002/iid3.563.
  19. Boucher BA, Wood GC, Swanson JM. Pharmacokinetic changes in critical illness. Crit Care Clin 2006;22(2):255–271, vi. DOI: 10.1016/j.ccc.2006.02.011.
  20. 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.
  21. Veiga VC, Prats JAGG, Farias DLC, Rosa RG, Dourado LK, Zampieri FG, et al. Effect of tocilizumab on clinical outcomes at 15 days in patients with severe or critical coronavirus disease 2019: Randomised controlled trial. BMJ 2021;372:n84. DOI: 10.1136/bmj.n84.
  22. 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(16):1503–1516. DOI: 10.1056/NEJMoa2028700.
  23. Salvarani C, Dolci G, Massari M, Merlo DF, Cavuto S, 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(1):24–31. DOI: 10.1001/jamainternmed.2020.6615.
  24. Perrone F, Piccirillo MC, Ascierto PA, Salvarani C, Parrella R, Marata AM, et al. Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial. J Transl Med 2020;18(1):405. DOI: 10.1186/s12967-020-02573-9.
  25. Wang D, Fu B, Peng Z, Yang D, Han M, Li M, et al. Tocilizumab in patients with moderate or severe COVID-19: A randomized, controlled, open-label, multicenter trial, Front Med 2021;15(3):486–494. DOI: 10.1007/s11684-020-0824-3.
  26. Zhao H, Zhu Q, Zhang C, Li J, Wei M, Qin Y, et al. Tocilizumab combined with favipiravir in the treatment of COVID-19: A multicenter trial in a small sample size. Biomed Pharmacother 2021;133:110825. DOI: 10.1016/j.biopha.2020.110825.
  27. Horby PW, Pessoa–Amorim G, Peto L, et al. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): A randomised, controlled, open-label, platform trial. Lancet 2021;397(10285): 1637–1645. DOI: 10.1016/S0140-6736(21)00676-0.
  28. Monedero P, Gea A, Castro P, Candela–Toha AM, Hernández–Sanz ML, Arruti E, et al. Early corticosteroids are associated with lower mortality in critically ill patients with COVID-19: A cohort study. Crit Care 2021;25(1):2. DOI: 10.1186/s13054-020-03422-3.
  29. Steinberg KP, Hudson LD, Goodman RB, Hough CL, Lanken PN, Hyzy R, et al. Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med 2006;354(16):1671–1684. DOI: 10.1056/NEJMoa051693.
  30. Kanberg N, Ashton NJ, Andersson LM, Yilmaz A, Lindh M, Nilsson S, et al. Neurochemical evidence of astrocytic and neuronal injury commonly found in COVID-19. Neurology 2020;95(12):e1754–e1759. DOI: 10.1212/wnl.0000000000010111.
  31. Virhammar J, Nääs A, Fällmar D, Cunningham JL, Klang A, Ashton NJ, et al. Biomarkers for central nervous system injury in cerebrospinal fluid are elevated in COVID-19 and associated with neurological symptoms and disease severity. Eur J Neurol 2020 28(10):3324–3331. DOI: 10.1111/ene.14703.
  32. Fällmar D, Rostami E, Kumlien E, Ashton NJ, Jackmann S, Pavel R, et al. The extent of neuroradiological findings in COVID-19 shows correlation with blood biomarkers, Glasgow coma scale score and days in ICU. J Neuroradiol 2021;S0150–9861(21)00167-X. DOI: 10.1016/j.neurad.2021.11.003.
  33. Ramiro S, Mostard RLM, Magro–Checa C, van Dongen CMP, Dormans T, Buijs J, et al. Historically controlled comparison of glucocorticoids with or without tocilizumab versus supportive care only in patients with COVID-19-associated cytokine storm syndrome: Results of the CHIC study. Ann Rheum Dis 2020;79(9):1143–1151. DOI: 10.1136/annrheumdis-2020-218479.
  34. Somers EC, Eschenauer GA, Troost JP, Golob JL, Gandhi TN, Wang L, et al. Tocilizumab for treatment of mechanically ventilated patients with COVID-19. Clin Infect Dis 2021;73(2):e445–e454. DOI: 10.1093/cid/ciaa954.
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