COVID-19’a Bağlı Sitokin Fırtınasında Anakinra ve Tosilizumab Tedavilerinin Karşılaştırılması

Year 2023, , 73 - 79, 20.01.2023

Ali Akın , Yılmaz Safi , Talat Soner Yılmaz

https://doi.org/10.33631/sabd.1119769

Abstract

Amaç: Koronavirüs-19 hastalığına (COVID-19) bağlı gelişen sitokin fırtınasının (SF) mortalite ve morbiditeyi etkilemede önemli olduğu düşünülmektedir. Çalışmamızda yoğun bakım kliniğinde SF nedenli yatan hastalarda tosilizumab ile anakinranın etkinliklerinin karşılaştırılması amaçlanmıştır.
Gereç ve Yöntemler: Çalışmaya Ocak 2021-Aralık 2021 tarihleri arasında SF gelişen 69 hasta alındı. Anakinra veya tosilizumab tedavisi alan hastaların aldıkları tedavi süreleri ve dozları, daha önce aldıkları tedaviler (favipiravir ve pulse steroid) kayıt altına alındı. Hastaların biyokimyasal parametreleri retrospektif olarak incelendi.
Bulgular: Sitokin fırtınası olan olguların 42’si (% 60,9) anakinra, 27’si (% 39,1) tosilizumab kullanmıştı. Olguların % 39,1’i (n=27) kadın, % 60,9’u (n=42) erkekti. Olguların yaşları 27 ile 89 arasında değişmekte olup, ortalama yaş 56,27±13,87 yıl olarak saptandı. İki grup arasında tedavi öncesi ve 48. saatte bakılan; beyaz küre (Wbc), lenfosit, nötrofil, ferritin, C Reaktif Protein (CRP), prokalsitonin, fibrinojen, D-dimer, kreatinin değerleri benzerdi (p> 0,05). Anakinra tedavisi alan 42 hastanın 21’i (% 50) exitus oldu, 21’i (% 50) servise alındı. Tosilizumab tedavisi alan 27 hastanın 23’ü (% 85,2) exitus oldu, 4’ü (% 14,8) servise alındı. Anakinra ve tosilizumab arasında mortalite açısından anlamlı fark olduğu tespit edildi (p= 0,014).
Sonuç: Çalışmamızda COVID-19 nedenli SF gelişen hastalarda anakinra tedavisi, tosilizumaba göre mortalite açısından üstün bulunmuştur.

Keywords

Covid-19, Sitokin Fırtınası, Anakinra, Tosilizumab

Comparison of Anakinra and Tocilizumab Treatments in Cytokine Storm Due to COVID-19

Abstract

Aim: It is thought that cytokine storm (CS) developing due to Coronavirus-19 disease (COVID-19) is important in affecting mortality and morbidity. In our study, it was aimed to compare the efficacy of tocilizumab and anakinra in patients hospitalized with CS in the intensive care clinic.
Material and Methods: Between January 2021 and December 2021, 69 patients who were developed CS were included in the study. Treatment durations and doses who received anakinra or tocilizumab treatment, and previous treatments (favipiravir and pulse steroids) were recorded. Biochemical parameters of the patients were retrospectively analyzed.
Results: Of the cases with CS, 42 (60.9%) received anakinra and 27 (39.1%) tocilizumab. Of the cases, 39.1% (n=27) were female and 60.9% (n=42) were male. The ages of the cases ranged from 27 to 89 years, and the mean age was 56.27±13.87 years. Between the two groups, before treatment and at the 48th hour; white blood cell (Wbc), lymphocyte, neutrophil, ferritin, C Reactive Protein (CRP), procalcitonin, fibrinogen, D-dimer, creatinine values were similar (p> 0.05). Of the 42 patients who received anakinra treatment, 21 (50%) died, and 21 (50%) were taken to the ward. Of 27 patients who received tocilizumab treatment, 23 (85.2%) died, and 4 (14.8%) were taken to the ward. There was a significant difference in mortality between anakinra and tocilizumab (p= 0.014).
Conclusion: In our study, anakinra treatment was found to be superior to tocilizumab in terms of mortality in patients who developed CS.

Keywords

Covid-19, Cytokine Storm, Anakinra, Tosilizumab

References

• World Health Organization. Director-General's remarks at the media briefing on 2019-nCoV on 11 February 2020. http://www.who.int/dg/speeches/detail/who-director-general-s-remarks-at-the-media-briefing-on-2019-ncov-on-11-february-2020 (Erişim Tarihi: 12.01. 2020).
• 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. Lancet. 2020; 395(10223): 497-506.
• Leisman D, Ronner L, Pinotti R, Taylor D, Sinha P, Calfee C, et al. Cytokine elevation in severe and critical COVID-19: a rapid systematic review, meta-analysis, and comparison with other inflammatory syndromes. The Lancet Respiratory Medicine. 2020; 8(12): 1233-44.
• Mehta P, McAuley D. F, Brownm M, Sanchez E, Tattersall R. S, Manson J. J. COVID-19: consider cytokine storm syndromes and immunosuppression. The lancet. 2020; 395(10229): 1033-4.
• Felsenstein S, Herbert J. A, McNamara P.S, Hedrich C.M. COVID-19: Immunology and treatment options. Clinical immunology. 2020; 215: 108448.
• Atkin-Smith G. K, Duan M, Chen W, Poon I. K. The induction and consequences of Influenza A virus-induced cell death. Cell death & disease. 2018; 9(10): 1-11.
• Zhang W, Zhao Y, Zhang F, Wang Q, Li T, Liu Z, et al. The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The Perspectives of clinical immunologists from China. Clinical immunology. 2020; 214: 108393.
• Salama C, Han J, Yau L, Reiss W. G, Kramer B, Neidhart J, et al. Tocilizumab in patients hospitalized with Covid-19 pneumonia. New England Journal of Medicine. 2021; 384(1): 20-30.
• Aouba A, Baldolli A, Geffray L, Verdon R, Bergot E, Martin-Silva N, et al. Targeting the inflammatory cascade with anakinra in moderate to severe COVID-19 pneumonia: case series. Annals of the rheumatic diseases. 2020; 79(10): 1381-2.
• Cavalli G, De Luca G, Campochiaro C, Della-Torre E, Ripa M, Canetti D, et al. Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study. The Lancet Rheumatology. 2020; 2(6): e325-e331.
• 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.
• Aomar-Millan I. F, Salvatierra J, Torres-Parejo U, Faro-Miguez N, Callejas-Rubio J. L, Ceballos-Torres A, et al. Anakinra after treatment with corticosteroids alone or with tocilizumab in patients with severe COVID-19 pneumonia and moderate hyperinflammation. A retrospective cohort study. Internal and emergency medicine. 2021; 16(4): 843-52.
• Langer-Gould A, Smith JB, Gonzales EG, Castillo RD, Figueroa JG, Ramanathan A, et al. Early identification of COVID-19 cytokine storm and treatment with anakinra or tocilizumab. International Journal of Infectious Diseases. 2020; 99: 291-7.
• Yuan J, Zou R, Zeng L, Kou S, Lan J, Li X, et al. The correlation between viral clearance and biochemical outcomes of 94 COVID‐19 infected discharged patients. Inflamm Res. 2020; 69(6): 599‐606.
• Pourbagheri-Sigaroodi A, Bashash D, Fateh F, Abolghasemi H. Laboratory findings in COVID-19 diagnosis and prognosis. Clinica Chimica Acta. 2020; 510: 475-82.
• Moore J. B, June C. H. Cytokine release syndrome in severe COVID-19. Science. 2020; 368(6490): 473-4.
• Galvan-Roman J. M, Rodriguez-Garcia S. C, Roy-Vallejo E, Marcos-Jimenez A, Sanchez-Alonso S, Fernandez-Diaz C, et al. IL-6 serum levels predict severity and response to tocilizumab in COVID-19: An observational study. Journal of Allergy and Clinical Immunology. 2021; 147(1): 72-80.
• Mazzoni A, Salvati L, Maggi L, Capone M, Vanni A, Spinicci M, et al. Impaired immune cell cytotoxicity in severe COVID-19 is IL-6 dependent. The Journal of clinical investigation. 2020; 130(9): 4694-703.
• Iglesias-Julian E, Lopez-Veloso M, de-la-Torre-Ferrera N, Barraza-Vengoechea J. C, Delgado-Lopez PD, Colazo-Burlato, et al. High dose subcutaneous Anakinra to treat acute respiratory distress syndrome secondary to cytokine storm syndrome among severely ill COVID-19 patients. Journal of autoimmunity. 2020; 115: 102537.
• Cauchois R, Koubi M, Delarbre D, Manet C, Carvelli J, Blasco V. B, et al. Early IL-1 receptor blockade in severe inflammatory respiratory failure complicating COVID-19. Proceedings of the National Academy of Sciences. 2020; 117(32): 18951-3.