Abstract
Amaç: Bu çalışmanın amacı anakinra ve tocilizumab tedavisi alan ağır ve kritik koronavirüs hastalığı 2019 (coronavirus disease 2019, COVID-19) hastalarında; endotrakeal entübasyon, non-invaziv mekanik ventilasyon, yüksek akım oksijen tedavisi gereksinimleri ve 28 günlük mortalite oranları arasında bir farklılık olup olmadığının araştırılmasıdır.
Gereç ve Yöntemler: Bu geriye dönük çalışmaya, Nisan 2020 ile Mart 2021 tarihleri arasında Karabük Eğitim ve Araştırma Hastanesi'nde tocilizumab ve anakinra ile tedavi edilmiş olan COVID-19 ile enfekte 70 hasta dahil edildi. Hastaların demografik özellikleri, komorbiditeler, tedaviler, hastaların klinik sonuçları ve hemogram bulguları ile ilgili veriler hastane kayıtlarından alındı.
Bulgular: Hastaların ortalama yaşı 61,34±11,8 yıl idi. 70 hastanın 12 (%17,1)’si kadın ve 58 (%82,9)’i erkekti. Ağır ve kritik COVID-19 vakası sırasıyla 48 (%68,6) hastada ve 22 (%31,4) hastada görüldü. Tocilizumab ve anakinra grupları arasında; 28 gündeki mortalite oranı istatistiksel olarak anlamlı şekilde farklı değildi (p=0,999). Yüksek akım oksijen tedavisi ve non-invaziv mekanik ventilasyon gereksinimlerinin her ikisi de tocilizumab grubunda anakinra grubundan daha düşük (sırasıyla p<0,001 ve p=0,002) iken entübasyon ihtiyacı bakımından iki grup arasında istatistiksel olarak anlamlı bir farklılık yoktu (p=0,999). Tocilizumab grubunda hastanede kalış süresi de anlamlı olarak daha kısaydı (p=0,027).
Sonuç: Tocilizumab grubunda yüksek akım oksijen tedavisi, non-invaziv mekanik ventilasyon gereksinimleri ve hastanede kalış süresi anakinra grubuna göre anlamlı derecede daha düşüktür. COVID-19'da sitokin fırtınası, aşırı inflamatuar yanıt, ciddi hastalık seyrine neden olmakta ve prognozu kötüleştirmektedir.
Keywords
References
- Cascella M, Rajnik M, Aleem A, Dulebohn SC, Di Napoli R. Features, evaluation, and treatment of coronavirus (COVID-19). 2022 Feb 5. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022.
- The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group, Sterne JAC, Murthy S, Diaz JV, Slutsky AS, Villar J, et al. Association between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: a meta-analysis. JAMA. 2020;324(13):1330-41.
- Erçen Diken Ö, Yıldırım F, Yıldız Gülhan P, Özkaya Ş, Şimşek M, Yücel C, et al. Corticosteroid use in COVID-19 pneumonia. Tuberk Toraks. 2021;69(2):217-26.
- Argüder E, Yanık Üstüner G, Ekici R, Kılıç H, Erten Ş, Karalezli A. Tuberculosis risk in patients with rheumatologic disease treated with biologic drugs. Tuberk Toraks. 2020;68(3):236-44.
- Fleischmann RM, Schechtman J, Bennett R, Handel ML, Burmester GR, Tesser J, et al. Anakinra, a recombinant human interleukin-1 receptor antagonist (r-metHuIL-1ra), in patients with rheumatoid arthritis: A large, international, multicenter, placebo-controlled trial. Arthritis Rheum. 2003;48(4):927-34.
- Yalçın Kehribar D, Özgen M. The experience of interleukin-1 inhibition in patients with familial Mediterranean fever. J Exp Clin Med. 2021;38(1):27-31.
- Yakar Hİ, Pazarlı AC, İnönü Köseoğlu H, Kanbay A. The effect of tocilizumab on severe COVID-19 infection: Review of current evidence. Tuberk Toraks. 2021;69(1):74-83.
- 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(1):20-30.
- Franzetti M, Forastieri A, Borsa N, Pandolfo A, Molteni C, Borghesi L, et al. IL-1 receptor antagonist anakinra in the treatment of COVID-19 acute respiratory distress syndrome: A retrospective, observational study. J Immunol. 2021;206(7):1569-75.
- Fan E, Brodie D, Slutsky AS. Acute respiratory distress syndrome: advances in diagnosis and treatment. JAMA. 2018;319(7):698-710.
- Xu YH, Dong JH, An WM, Lv XY, Yin XP, Zhang JZ, et al. Clinical and computed tomographic imaging features of novel coronavirus pneumonia caused by SARS-CoV-2. J Infect. 2020;80(4):394-400.
- 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. 2020;117(20):10970-5.
- Navarro‐Millán I, Sattui SE, Lakhanpal A, Zisa D, Siegel CH, Crow MK. Use of anakinra to prevent mechanical ventilation in severe COVID‐19: A case series. Arthritis Rheumatol. 2020;72(12):1990-7.
- Guaraldi G, Meschiari M, Cozzi-Lepri A, Milic J, Tonelli R, Menozzi M, et al. Tocilizumab in patients with severe COVID19: a retrospective cohort study. Lancet Rheumatol. 2020;2(8):e474-84.
- Knorr JP, Colomy V, Mauriello CM, Ha S. Tocilizumab in patients with severe COVID-19: A single-center observational analysis. J Med Virol. 2020;92(11):2813-20.
- 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.
- 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. Lancet Rheumatol. 2020;2(6):e325-31.
- Coloretti I, Busani S, Biagioni E, Venturelli S, Munari E, Sita M, et al. Effects of cytokine blocking agents on hospital mortality in patients admitted to ICU with acute respiratory distress syndrome by SARS-CoV-2 infection: retrospective cohort study. Multidiscip Respir Med. 2021;16(1):737.
- Aomar-Millán IF, Salvatierra J, Hernández-Quero J. Anakinra after treatment with corticosteroids alone or with tocilizumab in patients with severe COVID-19 pneumonia and moderate hyperinflammation. A retrospective cohort study: reply. Intern Emerg Med. 2021;16(4):1105-6.
- Pasin L, Cavalli G, Navalesi P, Sella N, Landoni G, Yavorovskiy AG, et al. Anakinra for patients with COVID-19: a meta-analysis of non-randomized cohort studies. Eur J Intern Med. 2021;86:34-40.
- Patoulias D, Dimosiari A, Michailidis T. Anakinra or tocilizumab for prevention of COVID-19 death? A big dilemma. Eur J Intern Med. 2021;90:107-8.
Abstract
Aim: The aim of this study was to examine whether a difference between endotracheal intubation, non-invasive mechanical ventilation, high flow oxygen therapy requirements and 28-day mortality rate in severe and critical coronavirus disease 2019 (COVID-19) patients receiving anakinra and tocilizumab treatment.
Material and Methods: A total of 70 patients infected with COVID-19, who were treated with tocilizumab and anakinra from April 2020 to March 2021 at Karabük Training and Research Hospital, were recruited in this retrospective study. Data on patient demographics, comorbidities, treatments, clinical outcomes of the patients’ and hemogram findings were retrieved from hospital records.
Results: The mean age of the patients was 61.34±11.8 years. Of the 70 patients, 12 (17.1%) were female and 58 (82.9%) were male. Severe and critical COVID-19 cases were evident in 48 (68.6%), and 22 (31.4%) patients, respectively. The mortality rate in 28 days was not statistically significantly different between the tocilizumab and anakinra groups (p=0.999). Both the necessity of high flow oxygen therapy and non-invasive mechanical ventilation were lower in the tocilizumab group than in the anakinra group (p<0.001, and p=0.002, respectively), while there was no statistically significant difference in the necessity of intubation between the two groups (p=0.999). The length of stay was also significantly shorter in the tocilizumab group (p=0.027).
Conclusion: High flow oxygen therapy, non-invasive mechanical ventilation requirements, and length of stay were significantly lower than anakinra in the tocilizumab group. Excessive inflammatory response with cytokine storm features causes severe disease course and worsens prognosis in COVID-19.
Keywords
References
- Cascella M, Rajnik M, Aleem A, Dulebohn SC, Di Napoli R. Features, evaluation, and treatment of coronavirus (COVID-19). 2022 Feb 5. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022.
- The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group, Sterne JAC, Murthy S, Diaz JV, Slutsky AS, Villar J, et al. Association between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: a meta-analysis. JAMA. 2020;324(13):1330-41.
- Erçen Diken Ö, Yıldırım F, Yıldız Gülhan P, Özkaya Ş, Şimşek M, Yücel C, et al. Corticosteroid use in COVID-19 pneumonia. Tuberk Toraks. 2021;69(2):217-26.
- Argüder E, Yanık Üstüner G, Ekici R, Kılıç H, Erten Ş, Karalezli A. Tuberculosis risk in patients with rheumatologic disease treated with biologic drugs. Tuberk Toraks. 2020;68(3):236-44.
- Fleischmann RM, Schechtman J, Bennett R, Handel ML, Burmester GR, Tesser J, et al. Anakinra, a recombinant human interleukin-1 receptor antagonist (r-metHuIL-1ra), in patients with rheumatoid arthritis: A large, international, multicenter, placebo-controlled trial. Arthritis Rheum. 2003;48(4):927-34.
- Yalçın Kehribar D, Özgen M. The experience of interleukin-1 inhibition in patients with familial Mediterranean fever. J Exp Clin Med. 2021;38(1):27-31.
- Yakar Hİ, Pazarlı AC, İnönü Köseoğlu H, Kanbay A. The effect of tocilizumab on severe COVID-19 infection: Review of current evidence. Tuberk Toraks. 2021;69(1):74-83.
- 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(1):20-30.
- Franzetti M, Forastieri A, Borsa N, Pandolfo A, Molteni C, Borghesi L, et al. IL-1 receptor antagonist anakinra in the treatment of COVID-19 acute respiratory distress syndrome: A retrospective, observational study. J Immunol. 2021;206(7):1569-75.
- Fan E, Brodie D, Slutsky AS. Acute respiratory distress syndrome: advances in diagnosis and treatment. JAMA. 2018;319(7):698-710.
- Xu YH, Dong JH, An WM, Lv XY, Yin XP, Zhang JZ, et al. Clinical and computed tomographic imaging features of novel coronavirus pneumonia caused by SARS-CoV-2. J Infect. 2020;80(4):394-400.
- 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. 2020;117(20):10970-5.
- Navarro‐Millán I, Sattui SE, Lakhanpal A, Zisa D, Siegel CH, Crow MK. Use of anakinra to prevent mechanical ventilation in severe COVID‐19: A case series. Arthritis Rheumatol. 2020;72(12):1990-7.
- Guaraldi G, Meschiari M, Cozzi-Lepri A, Milic J, Tonelli R, Menozzi M, et al. Tocilizumab in patients with severe COVID19: a retrospective cohort study. Lancet Rheumatol. 2020;2(8):e474-84.
- Knorr JP, Colomy V, Mauriello CM, Ha S. Tocilizumab in patients with severe COVID-19: A single-center observational analysis. J Med Virol. 2020;92(11):2813-20.
- 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.
- 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. Lancet Rheumatol. 2020;2(6):e325-31.
- Coloretti I, Busani S, Biagioni E, Venturelli S, Munari E, Sita M, et al. Effects of cytokine blocking agents on hospital mortality in patients admitted to ICU with acute respiratory distress syndrome by SARS-CoV-2 infection: retrospective cohort study. Multidiscip Respir Med. 2021;16(1):737.
- Aomar-Millán IF, Salvatierra J, Hernández-Quero J. Anakinra after treatment with corticosteroids alone or with tocilizumab in patients with severe COVID-19 pneumonia and moderate hyperinflammation. A retrospective cohort study: reply. Intern Emerg Med. 2021;16(4):1105-6.
- Pasin L, Cavalli G, Navalesi P, Sella N, Landoni G, Yavorovskiy AG, et al. Anakinra for patients with COVID-19: a meta-analysis of non-randomized cohort studies. Eur J Intern Med. 2021;86:34-40.
- Patoulias D, Dimosiari A, Michailidis T. Anakinra or tocilizumab for prevention of COVID-19 death? A big dilemma. Eur J Intern Med. 2021;90:107-8.
Details
| Primary Language | English |
|---|---|
| Subjects | Clinical Sciences |
| Journal Section | Research Article |
| Authors | |
| Publication Date | August 30, 2022 |
| Submission Date | March 7, 2022 |
| Published in Issue | Year 2022 Volume: 24 Issue: 2 |
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